ABSTRACT
Crystallography at low resolution must determine the atomic model from less experimental observations, which is challenging in the absence of a model. In addition, model bias is more severe when independent experimental data are scarce. Our methods solve the phase problem by combining the location of accurate model fragments using Phaser with density modification and interpretation of the resulting maps using SHELXE. From a partial, correct structure, the density modification process and the stereochemical constraints draw the rest of the structure, validating the result. This same principle is now exploited at low resolution. Coiled coils are important, ubiquitous structures but notoriously difficult to phase and to predict. Both correct solutions and incorrect ones are poorly discriminated by the crystallographic figures of merit as long as helices are correctly oriented. We incorporate coiled-coil verification, designed to set up competing, incompatible structural hypotheses to probe both the results and establish the power of the data to discriminate them. Efficiency of coiled-coil phasing and validation in test cases from 3 to 4 Å is demonstrated in ARCIMBOLDO_LITE, placing single helices, and in ARCIMBOLDO_SHREDDER, with fragments derived from AlphaFold models. SHELXE tracing at low resolution has been enhanced, maintaining its local character but extending the environment assessment. For non-helical structures, verification is demonstrated in the fragment location process. Its use is exemplified with the solution of the VSR1 structure at 3.5 Å, depending on LLG optimization and the emergence of new features in the electron density. Relying on verification, we have extended the use of the ARCIMBOLDO software to low resolution.
Subject(s)
Models, Molecular , Proteins , Proteins/chemistry , Crystallography, X-Ray , Protein Conformation , SoftwareABSTRACT
XDSGUI is a lightweight graphical user interface (GUI) for the XDS, SHELX and ARCIMBOLDO program packages that serves both novice and experienced users in obtaining optimal processing and phasing results for X-ray, neutron and electron diffraction data. The design of the program enables data processing and phasing without command line usage, and supports advanced command flows in a simple user-modifiable and user-extensible way. The GUI supplies graphical information based on the tabular log output of the programs, which is more intuitive, comprehensible and efficient than text output can be.
ABSTRACT
Reading bodies and faces is essential for efficient social interactions, though it may be thought-provoking for individuals with depression. Yet aberrations in the face sensitivity and underwriting neural circuits are not well understood, in particular, in male depression. Here, we use cutting-edge analyses of time course and dynamic topography of gamma oscillatory neuromagnetic cortical activity during administration of a task with Arcimboldo-like images. No difference in face tuning was found between individuals with depression and their neurotypical peers. Furthermore, this behavioral outcome nicely dovetails with magnetoencephalographic data: at early processing stages, the gamma oscillatory response to images resembling a face was rather similar in patients and controls. These bursts originated primarily from the right medioventral occipital cortex and lateral occipital cortex. At later processing stages, however, its topography altered remarkably in depression with profound engagement of the frontal circuits. Yet the primary difference in depressive individuals as compared with their neurotypical peers occurred over the left middle temporal cortices, a part of the social brain, engaged in feature integration and meaning retrieval. The outcome suggests compensatory recruitment of neural resources in male depression.
Subject(s)
Brain , Depression , Humans , Male , Brain/physiology , Magnetoencephalography , Occipital Lobe/physiology , Temporal Lobe/physiology , Brain MappingABSTRACT
Structure predictions have matched the accuracy of experimental structures from close homologues, providing suitable models for molecular replacement phasing. Even in predictions that present large differences due to the relative movement of domains or poorly predicted areas, very accurate regions tend to be present. These are suitable for successful fragment-based phasing as implemented in ARCIMBOLDO. The particularities of predicted models are inherently addressed in the new predicted_model mode, rendering preliminary treatment superfluous but also harmless. B-value conversion from predicted LDDT or error estimates, the removal of unstructured polypeptide, hierarchical decomposition of structural units from domains to local folds and systematically probing the model against the experimental data will ensure the optimal use of the model in phasing. Concomitantly, the exhaustive use of models and stereochemistry in phasing, refinement and validation raises the concern of crystallographic model bias and the need to critically establish the information contributed by the experiment. Therefore, in its predicted_model mode ARCIMBOLDO_SHREDDER will first determine whether the input model already constitutes a solution or provides a straightforward solution with Phaser. If not, extracted fragments will be located. If the landscape of solutions reveals numerous, clearly discriminated and consistent probes or if the input model already constitutes a solution, model-free verification will be activated. Expansions with SHELXE will omit the partial solution seeding phases and all traces outside their respective masks will be combined in ALIXE, as far as consistent. This procedure completely eliminates the molecular replacement search model in favour of the inferences derived from this model. In the case of fragments, an incorrect starting hypothesis impedes expansion. The predicted_model mode has been tested in different scenarios.
Subject(s)
Peptides , Crystallography, X-Ray , Models, MolecularABSTRACT
The plant-specific class XI myosins (MyoXIs) play key roles at the molecular, cellular and tissue levels, engaging diverse adaptor proteins to transport cargoes along actin filaments. To recognize their cargoes, MyoXIs have a C-terminal globular tail domain (GTD) that is evolutionarily related to those of class V myosins (MyoVs) from animals and fungi. Despite recent advances in understanding the functional roles played by MyoXI in plants, the structure of its GTD, and therefore the molecular determinants for cargo selectivity and recognition, remain elusive. In this study, the first crystal structure of a MyoXI GTD, that of MyoXI-K from Arabidopsis thaliana, was elucidated at 2.35â Å resolution using a low-identity and fragment-based phasing approach in ARCIMBOLDO_SHREDDER. The results reveal that both the composition and the length of the α5-α6 loop are distinctive features of MyoXI-K, providing evidence for a structural stabilizing role for this loop, which is otherwise carried out by a molecular zipper in MyoV GTDs. The crystal structure also shows that most of the characterized cargo-binding sites in MyoVs are not conserved in plant MyoXIs, pointing to plant-specific cargo-recognition mechanisms. Notably, the main elements involved in the self-regulation mechanism of MyoVs are conserved in plant MyoXIs, indicating this to be an ancient ancestral trait.
Subject(s)
Arabidopsis Proteins/chemistry , Arabidopsis/metabolism , Models, Molecular , Myosins/chemistry , Protein Conformation , Binding Sites , Protein DomainsABSTRACT
Structure determination of novel biological macromolecules by X-ray crystallography can be facilitated by the use of small structural fragments, some of only a few residues in length, as effective search models for molecular replacement to overcome the phase problem. Independence from the need for a complete pre-existing model with sequence similarity to the crystallized molecule is the primary appeal of ARCIMBOLDO, a suite of programs which employs this ab initio algorithm for phase determination. Here, the use of ARCIMBOLDO is investigated to overcome the phase problem with the electron cryomicroscopy (cryoEM) method known as microcrystal electron diffraction (MicroED). The results support the use of the ARCIMBOLDO_SHREDDER pipeline to provide phasing solutions for a structure of proteinase K from 1.6â Å resolution data using model fragments derived from the structures of proteins sharing a sequence identity of as low as 20%. ARCIMBOLDO_SHREDDER identified the most accurate polyalanine fragments from a set of distantly related sequence homologues. Alternatively, such templates were extracted in spherical volumes and given internal degrees of freedom to refine towards the target structure. Both modes relied on the rotation function in Phaser to identify or refine fragment models and its translation function to place them. Model completion from the placed fragments proceeded through phase combination of partial solutions and/or density modification and main-chain autotracing using SHELXE. The combined set of fragments was sufficient to arrive at a solution that resembled that determined by conventional molecular replacement using the known target structure as a search model. This approach obviates the need for a single, complete and highly accurate search model when phasing MicroED data, and permits the evaluation of large fragment libraries for this purpose.
Subject(s)
Endopeptidase K/chemistry , Models, Molecular , Software , Computer Simulation , Crystallography, X-Ray , Protein ConformationABSTRACT
Fragment-based molecular replacement exploits the use of very accurate yet incomplete search models. In the case of the ARCIMBOLDO programs, consistent phase sets produced from the placement and refinement of fragments with Phaser can be combined in order to increase their signal before proceeding to the step of density modification and autotracing with SHELXE. The program ALIXE compares multiple phase sets, evaluating mean phase differences to determine their common origin, and subsequently produces sets of combined phases that group consistent solutions. In this work, its use on different scenarios of very partial molecular-replacement solutions and its performance after the development of a much-optimized set of algorithms are described. The program is available both standalone and integrated within the ARCIMBOLDO programs. ALIXE has been analysed to identify its rate-limiting steps while exploring the best parameterization to improve its performance and make this software efficient enough to work on modest hardware. The algorithm has been parallelized and redesigned to meet the typical landscape of solutions. Analysis of pairwise correlation between the phase sets has also been explored to test whether this would provide additional insight. ALIXE can be used to exhaustively analyse all partial solutions produced or to complement those already selected for expansion, and also to reduce the number of redundant solutions, which is particularly relevant to the case of coiled coils, or to combine partial solutions from different programs. In each case parallelization and optimization to provide speedup makes its use amenable to typical hardware found in crystallography. ARCIMBOLDO_BORGES and ARCIMBOLDO_SHREDDER now call on ALIXE by default.
Subject(s)
Algorithms , Crystallography, X-Ray/methods , Software , Models, Molecular , Molecular StructureABSTRACT
Fragment-based molecular-replacement methods can solve a macromolecular structure quasi-ab initio. ARCIMBOLDO, using a common secondary-structure or tertiary-structure template or a library of folds, locates these with Phaser and reveals the rest of the structure by density modification and autotracing in SHELXE. The latter stage is challenging when dealing with diffraction data at lower resolution, low solvent content, high ß-sheet composition or situations in which the initial fragments represent a low fraction of the total scattering or where their accuracy is low. SEQUENCE SLIDER aims to overcome these complications by extending the initial polyalanine fragment with side chains in a multisolution framework. Its use is illustrated on test cases and previously unknown structures. The selection and order of fragments to be extended follows the decrease in log-likelihood gain (LLG) calculated with Phaser upon the omission of each single fragment. When the starting substructure is derived from a remote homolog, sequence assignment to fragments is restricted by the original alignment. Otherwise, the secondary-structure prediction is matched to that found in fragments and traces. Sequence hypotheses are trialled in a brute-force approach through side-chain building and refinement. Scoring the refined models through their LLG in Phaser may allow discrimination of the correct sequence or filter the best partial structures for further density modification and autotracing. The default limits for the number of models to pursue are hardware dependent. In its most economic implementation, suitable for a single laptop, the main-chain trace is extended as polyserine rather than trialling models with different sequence assignments, which requires a grid or multicore machine. SEQUENCE SLIDER has been instrumental in solving two novel structures: that of MltC from 2.7â Å resolution data and that of a pneumococcal lipoprotein with 638 residues and 35% solvent content.
Subject(s)
Crystallography, X-Ray/methods , Peptide Fragments/chemistry , Peptides/chemistry , Software , Algorithms , Glycosyltransferases/chemistry , Lipoproteins/chemistry , Protein Folding , Protein Structure, SecondaryABSTRACT
Many biologists are now routinely seeking to determine the three-dimensional structures of their proteins of choice, illustrating the importance of this knowledge, but also of the simplification and streamlining of structure-determination processes. Despite the fact that most software packages offer simple pipelines, for the non-expert navigating the outputs and understanding the key aspects can be daunting. Here, the structure determination of the type IV pili (TFP) protein PilA1 from Clostridioides difficile is used to illustrate the different steps involved, the key decision criteria and important considerations when using the most common pipelines and software. Molecular-replacement pipelines within CCP4i2 are presented to illustrate the more commonly used processes. Previous knowledge of the biology and structure of TFP pilins, particularly the presence of a long, N-terminal α-helix required for pilus formation, allowed informed decisions to be made during the structure-determination strategy. The PilA1 structure was finally successfully determined using ARCIMBOLDO and the ab initio MR strategy used is described.
Subject(s)
Bacterial Proteins/chemistry , Clostridiales/chemistry , Fimbriae Proteins/chemistry , Protein Conformation, alpha-Helical , Protein Structure, Tertiary , SoftwareABSTRACT
Crystal structure determination requires solving the phase problem. This can be accomplished using ab initio direct methods for small molecules and macromolecules at resolutions higher than 1.2â Å, whereas macromolecular structure determination at lower resolution requires either molecular replacement using a homologous structure or experimental phases using a derivative such as covalent labeling (for example selenomethionine or mercury derivatization) or heavy-atom soaking (for example iodide ions). Here, a case is presented in which crystals were obtained from a 30.8â kDa protein sample and yielded a 1.6â Å resolution data set with a unit cell that could accommodate approximately 8â kDa of protein. Thus, it was unclear what had been crystallized. Molecular replacement with pieces of homologous proteins and attempts at iodide ion soaking failed to yield a solution. The crystals could not be reproduced. Sequence-independent molecular replacement using the structures available in the Protein Data Bank also failed to yield a solution. Ultimately, ab initio structure solution proved successful using the program ARCIMBOLDO, which identified two α-helical elements and yielded interpretable maps. The structure was the C-terminal dimerization domain of the intended target from Mycobacterium smegmatis. This structure is presented as a user-friendly test case in which an unknown protein fragment could be determined using ARCIMBOLDO.
Subject(s)
Bacterial Proteins/chemistry , GTP Phosphohydrolases/chemistry , Guanosine Diphosphate/chemistry , Mycobacterium smegmatis/chemistry , Peptide Fragments/chemistry , Software , Amino Acid Sequence , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Binding Sites , Cloning, Molecular , Crystallography, X-Ray , Databases, Protein , Escherichia coli/genetics , Escherichia coli/metabolism , GTP Phosphohydrolases/genetics , GTP Phosphohydrolases/metabolism , Gene Expression , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Guanosine Diphosphate/metabolism , Models, Molecular , Peptide Fragments/genetics , Peptide Fragments/metabolism , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Protein Multimerization , Proteolysis , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolismABSTRACT
Macromolecular structures can be solved by molecular replacement provided that suitable search models are available. Models from distant homologues may deviate too much from the target structure to succeed, notwithstanding an overall similar fold or even their featuring areas of very close geometry. Successful methods to make the most of such templates usually rely on the degree of conservation to select and improve search models. ARCIMBOLDO_SHREDDER uses fragments derived from distant homologues in a brute-force approach driven by the experimental data, instead of by sequence similarity. The new algorithms implemented in ARCIMBOLDO_SHREDDER are described in detail, illustrating its characteristic aspects in the solution of new and test structures. In an advance from the previously published algorithm, which was based on omitting or extracting contiguous polypeptide spans, model generation now uses three-dimensional volumes respecting structural units. The optimal fragment size is estimated from the expected log-likelihood gain (LLG) values computed assuming that a substructure can be found with a level of accuracy near that required for successful extension of the structure, typically below 0.6â Å root-mean-square deviation (r.m.s.d.) from the target. Better sampling is attempted through model trimming or decomposition into rigid groups and optimization through Phaser's gyre refinement. Also, after model translation, packing filtering and refinement, models are either disassembled into predetermined rigid groups and refined (gimble refinement) or Phaser's LLG-guided pruning is used to trim the model of residues that are not contributing signal to the LLG at the target r.m.s.d. value. Phase combination among consistent partial solutions is performed in reciprocal space with ALIXE. Finally, density modification and main-chain autotracing in SHELXE serve to expand to the full structure and identify successful solutions. The performance on test data and the solution of new structures are described.
Subject(s)
Algorithms , Macromolecular Substances/chemistry , Models, Molecular , Structural Homology, Protein , Bacterial Proteins/chemistry , Computer Simulation , Crystallography, X-RayABSTRACT
ARCIMBOLDO solves the phase problem by combining the location of small model fragments using Phaser with density modification and autotracing using SHELXE. Mainly helical structures constitute favourable cases, which can be solved using polyalanine helical fragments as search models. Nevertheless, the solution of coiled-coil structures is often complicated by their anisotropic diffraction and apparent translational noncrystallographic symmetry. Long, straight helices have internal translational symmetry and their alignment in preferential directions gives rise to systematic overlap of Patterson vectors. This situation has to be differentiated from the translational symmetry relating different monomers. ARCIMBOLDO_LITE has been run on single workstations on a test pool of 150 coiled-coil structures with 15-635 amino acids per asymmetric unit and with diffraction data resolutions of between 0.9 and 3.0â Å. The results have been used to identify and address specific issues when solving this class of structures using ARCIMBOLDO. Features from Phaser v.2.7 onwards are essential to correct anisotropy and produce translation solutions that will pass the packing filters. As the resolution becomes worse than 2.3â Å, the helix direction may be reversed in the placed fragments. Differentiation between true solutions and pseudo-solutions, in which helix fragments were correctly positioned but in a reverse orientation, was found to be problematic at resolutions worse than 2.3â Å. Therefore, after every new fragment-placement round, complete or sparse combinations of helices in alternative directions are generated and evaluated. The final solution is once again probed by helix reversal, refinement and extension. To conclude, density modification and SHELXE autotracing incorporating helical constraints is also exploited to extend the resolution limit in the case of coiled coils and to enhance the identification of correct solutions. This study resulted in a specialized mode within ARCIMBOLDO for the solution of coiled-coil structures, which overrides the resolution limit and can be invoked from the command line (keyword coiled_coil) or ARCIMBOLDO_LITE task interface in CCP4i.
Subject(s)
Computer Graphics , Computer Simulation , Protein Conformation , Proteins/analysis , Proteins/chemistry , Software , Crystallography, X-Ray , Humans , Models, Molecular , Protein DomainsABSTRACT
ARCIMBOLDO solves the phase problem at resolutions of around 2â Å or better through massive combination of small fragments and density modification. For complex structures, this imposes a need for a powerful grid where calculations can be distributed, but for structures with up to 200 amino acids in the asymmetric unit a single workstation may suffice. The use and performance of the single-workstation implementation, ARCIMBOLDO_LITE, on a pool of test structures with 40-120 amino acids and resolutions between 0.54 and 2.2â Å is described. Inbuilt polyalanine helices and iron cofactors are used as search fragments. ARCIMBOLDO_BORGES can also run on a single workstation to solve structures in this test set using precomputed libraries of local folds. The results of this study have been incorporated into an automated, resolution- and hardware-dependent parameterization. ARCIMBOLDO has been thoroughly rewritten and three binaries are now available: ARCIMBOLDO_LITE, ARCIMBOLDO_SHREDDER and ARCIMBOLDO_BORGES. The programs and libraries can be downloaded from http://chango.ibmb.csic.es/ARCIMBOLDO_LITE.
Subject(s)
Computers , Database Management Systems , Proteins/chemistry , Amino Acid Sequence , Models, Molecular , Molecular Sequence Data , Protein Conformation , SoftwareABSTRACT
ARCIMBOLDO allows ab initio phasing of macromolecular structures below atomic resolution by exploiting the location of small model fragments combined with density modification in a multisolution frame. The model fragments can be either secondary-structure elements predicted from the sequence or tertiary-structure fragments. The latter can be derived from libraries of typical local folds or from related structures, such as a low-homology model that is unsuccessful in molecular replacement. In all ARCIMBOLDO applications, fragments are searched for sequentially. Correct partial solutions obtained after each fragment-search stage but lacking the necessary phasing power can, if combined, succeed. Here, an analysis is presented of the clustering of partial solutions in reciprocal space and of its application to a set of different cases. In practice, the task of combining model fragments from an ARCIMBOLDO run requires their referral to a common origin and is complicated by the presence of correct and incorrect solutions as well as by their not being independent. The F-weighted mean phase difference has been used as a figure of merit. Clustering perfect, non-overlapping fragments dismembered from test structures in polar and nonpolar space groups shows that density modification before determining the relative origin shift enhances its discrimination. In the case of nonpolar space groups, clustering of ARCIMBOLDO solutions from secondary-structure models is feasible. The use of partially overlapping search fragments provides a more favourable circumstance and was assessed on a test case. Applying the devised strategy, a previously unknown structure was solved from clustered correct partial solutions.
Subject(s)
Macromolecular Substances/chemistry , Models, Molecular , Protein ConformationABSTRACT
A través de su técnica pictórica, Giuseppe Arcimboldo nos muestra cómo la solidaridad es un principio universal que logra que, de la armonía de la multiplicidad y diversidad de lo simple, pueda surgir la complejidad de lo grandioso. (AU)
Through his painting technique, Giuseppe Arcimboldo shows how solidarity is a universal principle that achieves the harmony of the multiplicity and diversity of the simple, from which may arise the complexity of the great. (AU)
Subject(s)
Humans , Art , Human Characteristics , Solidarity , Paintings/psychologyABSTRACT
Nuclear hormone receptors are cytoplasm-based transcription factors that bind a ligand, translate to the nucleus and initiate gene transcription in complex with a co-activator such as TIF2 (transcriptional intermediary factor 2). For structural studies the co-activator is usually mimicked by a peptide of circa 13 residues, which for the largest part forms an α-helix when bound to the receptor. The aim was to co-crystallize the glucocorticoid receptor in complex with a ligand and the TIF2 co-activator peptide. The 1.82â Å resolution diffraction data obtained from the crystal could not be phased by molecular replacement using the known receptor structures. HPLC analysis of the crystals revealed the absence of the receptor and indicated that only the co-activator peptide was present. The self-rotation function displayed 13-fold rotational symmetry, which initiated an exhaustive but unsuccessful molecular-replacement approach using motifs of 13-fold symmetry such as α- and ß-barrels in various geometries. The structure was ultimately determined by using a single α-helix and the software ARCIMBOLDO, which assembles fragments placed by PHASER before using them as seeds for density modification model building in SHELXE. Systematic variation of the helix length revealed upper and lower size limits for successful structure determination. A beautiful but unanticipated structure was obtained that forms superhelices with left-handed twist throughout the crystal, stabilized by ligand interactions. Together with the increasing diversity of structural elements in the Protein Data Bank the results from TIF2 confirm the potential of fragment-based molecular replacement to significantly accelerate the phasing step for native diffraction data at around 2â Å resolution.
ABSTRACT
Ab initio phasing of macromolecular structures, from the native intensities alone with no experimental phase information or previous particular structural knowledge, has been the object of a long quest, limited by two main barriers: structure size and resolution of the data. Current approaches to extend the scope of ab initio phasing include use of the Patterson function, density modification and data extrapolation. The authors' approach relies on the combination of locating model fragments such as polyalanine α-helices with the program PHASER and density modification with the program SHELXE. Given the difficulties in discriminating correct small substructures, many putative groups of fragments have to be tested in parallel; thus calculations are performed in a grid or supercomputer. The method has been named after the Italian painter Arcimboldo, who used to compose portraits out of fruit and vegetables. With ARCIMBOLDO, most collections of fragments remain a 'still-life', but some are correct enough for density modification and main-chain tracing to reveal the protein's true portrait. Beyond α-helices, other fragments can be exploited in an analogous way: libraries of helices with modelled side chains, ß-strands, predictable fragments such as DNA-binding folds or fragments selected from distant homologues up to libraries of small local folds that are used to enforce nonspecific tertiary structure; thus restoring the ab initio nature of the method. Using these methods, a number of unknown macromolecules with a few thousand atoms and resolutions around 2â Å have been solved. In the 2014 release, use of the program has been simplified. The software mediates the use of massive computing to automate the grid access required in difficult cases but may also run on a single multicore workstation (http://chango.ibmb.csic.es/ARCIMBOLDO_LITE) to solve straightforward cases.
ABSTRACT
Molecular replacement, one of the general methods used to solve the crystallographic phase problem, relies on the availability of suitable models for placement in the unit cell of the unknown structure in order to provide initial phases. ARCIMBOLDO, originally conceived for ab initio phasing, operates at the limit of this approach, using small, very accurate fragments such as polyalanine α-helices. A distant homolog may contain accurate building blocks, but it may not be evident which sub-structure is the most suitable purely from the degree of conservation. Trying out all alternative possibilities in a systematic way is computationally expensive, even if effective. In the present study, the solution of the previously unknown structure of MltE, an outer membrane-anchored endolytic peptidoglycan lytic transglycosylase from Escherichia coli, is described. The asymmetric unit contains a dimer of this 194 amino acid protein. The closest available homolog was the catalytic domain of Slt70 (PDB code 1QTE). Originally, this template was used omitting contiguous spans of aminoacids and setting as many ARCIMBOLDO runs as models, each aiming to locate two copies sequentially with PHASER. Fragment trimming against the correlation coefficient prior to expansion through density modification and autotracing in SHELXE was essential. Analysis of the figures of merit led to the strategy to optimize the search model against the experimental data now implemented within ARCIMBOLDO-SHREDDER (http://chango.ibmb.csic.es/SHREDDER). In this strategy, the initial template is systematically shredded, and fragments are scored against each unique solution of the rotation function. Results are combined into a score per residue and the template is trimmed accordingly.
Subject(s)
Escherichia coli Proteins/chemistry , Glycosyltransferases/chemistry , Models, Molecular , Peptide Fragments/chemistry , Software , Amino Acid Sequence , Catalytic Domain , Computer Simulation , Crystallography, X-Ray , Escherichia coli/enzymology , Molecular Sequence Data , Muramidase/chemistry , Protein Structure, Secondary , Structural Homology, ProteinABSTRACT
The properties of the face-sensitive N170 component of the event-related brain potential (ERP) were explored through an orientation discrimination task using natural faces, objects, and Arcimboldo paintings presented upright or inverted. Because Arcimboldo paintings are composed of non-face objects but have a global face configuration, they provide great control to disentangle high-level face-like or object-like visual processes at the level of the N170, and may help to examine the implication of each hemisphere in the global/holistic processing of face formats. For upright position, N170 amplitudes in the right occipito-temporal region did not differ between natural faces and Arcimboldo paintings but were larger for both of these categories than for objects, supporting the view that as early as the N170 time-window, the right hemisphere is involved in holistic perceptual processing of face-like configurations irrespective of their features. Conversely, in the left hemisphere, N170 amplitudes differed between Arcimboldo portraits and natural faces, suggesting that this hemisphere processes local facial features. For upside-down orientation in both hemispheres, N170 amplitudes did not differ between Arcimboldo paintings and objects, but were reduced for both categories compared to natural faces, indicating that the disruption of holistic processing with inversion leads to an object-like processing of Arcimboldo paintings due to the lack of local facial features. Overall, these results provide evidence that global/holistic perceptual processing of faces and face-like formats involves the right hemisphere as early as the N170 time-window, and that the local processing of face features is rather implemented in the left hemisphere.