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1.
ACS Photonics ; 9(11): 3617-3624, 2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36411820

RESUMO

Nanophotonic platforms in theory uniquely enable < femtomoles of chiral biological and pharmaceutical molecules to be detected, through the highly localized changes in the chiral asymmetries of the near fields that they induce. However, current chiral nanophotonic based strategies are intrinsically limited because they rely on far field optical measurements that are sensitive to a much larger near field volume, than that influenced by the chiral molecules. Consequently, they depend on detecting small changes in far field optical response restricting detection sensitivities. Here, we exploit an intriguing phenomenon, plasmonic circularly polarized luminescence (PCPL), which is an incisive local probe of near field chirality. This allows the chiral detection of monolayer quantities of a de novo designed peptide, which is not achieved with a far field response. Our work demonstrates that by leveraging the capabilities of nanophotonic platforms with the near field sensitivity of PCPL, optimal biomolecular detection performance can be achieved, opening new avenues for nanometrology.

2.
Science ; 376(6593): eabo0882, 2022 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-35536897

RESUMO

Tschauner et al. (Reports, 11 November 2021, p. 891) present evidence that diamond GRR-1507 formed in the lower mantle. Instead, the data support a much shallower origin in cold, subcratonic lithospheric mantle. X-ray diffraction data are well matched to phases common in microinclusion-bearing lithospheric diamonds. The calculated bulk inclusion composition is too imprecise to uniquely confirm CaSiO3 stoichiometry and is equally consistent with inclusions observed in other lithospheric diamonds.

3.
Nat Chem ; 13(7): 643-650, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33972753

RESUMO

The design of peptides that assemble in membranes to form functional ion channels is challenging. Specifically, hydrophobic interactions must be designed between the peptides and at the peptide-lipid interfaces simultaneously. Here, we take a multi-step approach towards this problem. First, we use rational de novo design to generate water-soluble α-helical barrels with polar interiors, and confirm their structures using high-resolution X-ray crystallography. These α-helical barrels have water-filled lumens like those of transmembrane channels. Next, we modify the sequences to facilitate their insertion into lipid bilayers. Single-channel electrical recordings and fluorescent imaging of the peptides in membranes show monodisperse, cation-selective channels of unitary conductance. Surprisingly, however, an X-ray structure solved from the lipidic cubic phase for one peptide reveals an alternative state with tightly packed helices and a constricted channel. To reconcile these observations, we perform computational analyses to compare the properties of possible different states of the peptide.


Assuntos
Canais Iônicos/química , Bicamadas Lipídicas/química , Peptídeos/química , Sequência de Aminoácidos , Simulação de Dinâmica Molecular , Conformação Proteica em alfa-Hélice , Engenharia de Proteínas , Solubilidade , Água/química
4.
Biomacromolecules ; 22(5): 2010-2019, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33881308

RESUMO

Rational protein design requires understanding the contribution of each amino acid to a targeted protein fold. For a subset of protein structures, namely, α-helical coiled coils (CCs), knowledge is sufficiently advanced to allow the rational de novo design of many structures, including entirely new protein folds. Current CC design rules center on using aliphatic hydrophobic residues predominantly to drive the folding and assembly of amphipathic α helices. The consequences of using aromatic residues-which would be useful for introducing structural probes, and binding and catalytic functionalities-into these interfaces are not understood. There are specific examples of designed CCs containing such aromatic residues, e.g., phenylalanine-rich sequences, and the use of polar aromatic residues to make buried hydrogen-bond networks. However, it is not known generally if sequences rich in tyrosine can form CCs, or what CC assemblies these would lead to. Here, we explore tyrosine-rich sequences in a general CC-forming background and resolve new CC structures. In one of these, an antiparallel tetramer, the tyrosine residues are solvent accessible and pack at the interface between the core and the surface. In another more complex structure, the residues are buried and form an extended hydrogen-bond network.


Assuntos
Dobramento de Proteína , Proteínas , Sequência de Aminoácidos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Estrutura Secundária de Proteína
5.
Org Lett ; 22(11): 4424-4428, 2020 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-32406695

RESUMO

We report a simple reductive amination protocol to ligate two peptides, while simultaneously installing a ß-turn mimic at the ligation junction. This strategy uses commercially available materials, mild chemical conditions, and a chemoselective ligation reaction of unprotected peptide substrates accessed through standard solid phase methods. This system was implemented in a designed ß-hairpin system, and biophysical analysis demonstrates effective mimicry of the ß-turn.

6.
J Am Chem Soc ; 141(22): 8787-8797, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31066556

RESUMO

The association of amphipathic α helices in water leads to α-helical-bundle protein structures. However, the driving force for this-the hydrophobic effect-is not specific and does not define the number or the orientation of helices in the associated state. Rather, this is achieved through deeper sequence-to-structure relationships, which are increasingly being discerned. For example, for one structurally extreme but nevertheless ubiquitous class of bundle-the α-helical coiled coils-relationships have been established that discriminate between all-parallel dimers, trimers, and tetramers. Association states above this are known, as are antiparallel and mixed arrangements of the helices. However, these alternative states are less well understood. Here, we describe a synthetic-peptide system that switches between parallel hexamers and various up-down-up-down tetramers in response to single-amino-acid changes and solution conditions. The main accessible states of each peptide variant are characterized fully in solution and, in most cases, to high resolution with X-ray crystal structures. Analysis and inspection of these structures helps rationalize the different states formed. This navigation of the structural landscape of α-helical coiled coils above the dimers and trimers that dominate in nature has allowed us to design rationally a well-defined and hyperstable antiparallel coiled-coil tetramer (apCC-Tet). This robust de novo protein provides another scaffold for further structural and functional designs in protein engineering and synthetic biology.


Assuntos
Proteínas/química , Sequência de Aminoácidos , Interações Hidrofóbicas e Hidrofílicas , Modelos Moleculares , Conformação Proteica em alfa-Hélice , Dobramento de Proteína , Água/química
7.
Nat Commun ; 9(1): 4132, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30297707

RESUMO

In coiled-coil (CC) protein structures α-helices wrap around one another to form rope-like assemblies. Most natural and designed CCs have two-four helices and cyclic (Cn) or dihedral (Dn) symmetry. Increasingly, CCs with five or more helices are being reported. A subset of these higher-order CCs is of interest as they have accessible central channels that can be functionalised; they are α-helical barrels. These extended cavities are surprising given the drive to maximise buried hydrophobic surfaces during protein folding and assembly in water. Here, we show that α-helical barrels can be maintained by the strategic placement of ß-branched aliphatic residues lining the lumen. Otherwise, the structures collapse or adjust to give more-complex multi-helix assemblies without Cn or Dn symmetry. Nonetheless, the structural hallmark of CCs-namely, knobs-into-holes packing of side chains between helices-is maintained leading to classes of CCs hitherto unobserved in nature or accessed by design.


Assuntos
Modelos Moleculares , Dobramento de Proteína , Multimerização Proteica , Estrutura Secundária de Proteína , Sequência de Aminoácidos , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Peptídeos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Água/química
8.
Sci Rep ; 8(1): 11753, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30082916

RESUMO

Thrombospondins (TSPs) are multidomain glycoproteins with complex matricellular functions in tissue homeostasis and remodeling. We describe a novel role of TSP as a Wnt signaling target in the basal eumetazoan Hydra. Proteome analysis identified Hydra magnipapillata TSP (HmTSP) as a major component of the cnidarian mesoglea. In general, the domain organization of cnidarian TSPs is related to the pentameric TSPs of bilaterians, and in phylogenetic analyses cnidarian TSPs formed a separate clade of high sequence diversity. HmTSP expression in polyps was restricted to the hypostomal tip and tentacle bases that harbor Wnt-regulated organizer tissues. In the hypostome, HmTSP- and Wnt3-expressing cells were identical or in close vicinity to each other, and regions of ectopic tentacle formation induced by pharmacological ß-Catenin activation (Alsterpaullone) corresponded to foci of HmTSP expression. Chromatin immunoprecipitation (ChIP) confirmed binding of Hydra TCF to conserved elements in the HmTSP promotor region. Accordingly, ß-Catenin knockdown by siRNAs reduced normal HmTSP expression at the head organizer. In contrast, knockdown of HmTSP expression led to increased numbers of ectopic organizers in Alsterpaullone-treated animals, indicating a negative regulatory function. Our data suggest an unexpected role for HmTSP as a feedback inhibitor of Wnt signaling during Hydra body axis patterning and maintenance.


Assuntos
Hydra/metabolismo , Proteoma/metabolismo , Trombospondinas/metabolismo , Animais , Padronização Corporal/genética , Padronização Corporal/fisiologia , Regiões Promotoras Genéticas/genética , Proteoma/genética , RNA Interferente Pequeno/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Trombospondinas/genética , Proteínas Wnt/genética , Proteínas Wnt/metabolismo , beta Catenina/genética , beta Catenina/metabolismo
9.
Bioinformatics ; 34(19): 3316-3323, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29722888

RESUMO

Motivation: To understand protein structure, folding and function fully and to design proteins de novo reliably, we must learn from natural protein structures that have been characterized experimentally. The number of protein structures available is large and growing exponentially, which makes this task challenging. Indeed, computational resources are becoming increasingly important for classifying and analyzing this resource. Here, we use tools from graph theory to define an Atlas classification scheme for automatically categorizing certain protein substructures. Results: Focusing on the α-helical coiled coils, which are ubiquitous protein-structure and protein-protein interaction motifs, we present a suite of computational resources designed for analyzing these assemblies. iSOCKET enables interactive analysis of side-chain packing within proteins to identify coiled coils automatically and with considerable user control. Applying a graph theory-based Atlas classification scheme to structures identified by iSOCKET gives the Atlas of Coiled Coils, a fully automated, updated overview of extant coiled coils. The utility of this approach is illustrated with the first formal classification of an emerging subclass of coiled coils called α-helical barrels. Furthermore, in the Atlas, the known coiled-coil universe is presented alongside a partial enumeration of the 'dark matter' of coiled-coil structures; i.e. those coiled-coil architectures that are theoretically possible but have not been observed to date, and thus present defined targets for protein design. Availability and implementation: iSOCKET is available as part of the open-source GitHub repository associated with this work (https://github.com/woolfson-group/isocket). This repository also contains all the data generated when classifying the protein graphs. The Atlas of Coiled Coils is available at: http://coiledcoils.chm.bris.ac.uk/atlas/app.


Assuntos
Dobramento de Proteína , Proteínas/química , Conformação Proteica em alfa-Hélice , Domínios e Motivos de Interação entre Proteínas
10.
Phys Chem Miner ; 45(4): 311-322, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31258241

RESUMO

ABF3 compounds have been found to make valuable low-pressure analogues for high-pressure silicate phases that are present in the Earth's deep interior and that may also occur in the interiors of exoplanets. The phase diagrams of two of these materials, KCaF3 and NaMgF3, have been investigated in detail by static ab initio computer simulations based on density functional theory. Six ABF3 polymorphs were considered, as follows: the orthorhombic perovskite structure (GdFeO3-type; space group Pbnm); the orthorhombic CaIrO3 structure (Cmcm; commonly referred to as the "post-perovskite" structure); the orthorhombic Sb2S3 and La2S3 structures (both Pmcn); the hexagonal structure previously suggested in computer simulations of NaMgF3 (P63/mmc); the monoclinic structure found to be intermediate between the perovskite and CaIrO3 structures in CaRhO3 (P21/m). Volumetric and axial equations of state of all phases considered are presented. For KCaF3, as expected, the perovskite phase is shown to be the most thermodynamically stable at atmospheric pressure. With increasing pressure, the relative stability of the KCaF3 phases then follows the sequence: perovskite â†’ La2S3 structure â†’ Sb2S3 structure â†’ P63/mmc structure; the CaIrO3 structure is never the most stable form. Above about 2.6 GPa, however, none of the KCaF3 polymorphs are stable with respect to dissociation into KF and CaF2. The possibility that high-pressure KCaF3 polymorphs might exist metastably at 300 K, or might be stabilised by chemical substitution so as to occur within the standard operating range of a multi-anvil press, is briefly discussed. For NaMgF3, the transitions to the high-pressure phases occur at pressures outside the normal range of a multi-anvil press. Two different sequences of transitions had previously been suggested from computer simulations. With increasing pressure, we find that the relative stability of the NaMgF3 phases follows the sequence: perovskite â†’ CaIrO3 structure â†’ Sb2S3 structure â†’ P63/mmc structure. However, only the perovskite and CaIrO3 structures are stable with respect to dissociation into NaF and MgF2.

11.
Philos Trans R Soc Lond B Biol Sci ; 372(1726)2017 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-28630153

RESUMO

The rational (de novo) design of membrane-spanning proteins lags behind that for water-soluble globular proteins. This is due to gaps in our knowledge of membrane-protein structure, and experimental difficulties in studying such proteins compared to water-soluble counterparts. One limiting factor is the small number of experimentally determined three-dimensional structures for transmembrane proteins. By contrast, many tens of thousands of globular protein structures provide a rich source of 'scaffolds' for protein design, and the means to garner sequence-to-structure relationships to guide the design process. The α-helical coiled coil is a protein-structure element found in both globular and membrane proteins, where it cements a variety of helix-helix interactions and helical bundles. Our deep understanding of coiled coils has enabled a large number of successful de novo designs. For one class, the α-helical barrels-that is, symmetric bundles of five or more helices with central accessible channels-there are both water-soluble and membrane-spanning examples. Recent computational designs of water-soluble α-helical barrels with five to seven helices have advanced the design field considerably. Here we identify and classify analogous and more complicated membrane-spanning α-helical barrels from the Protein Data Bank. These provide tantalizing but tractable targets for protein engineering and de novo protein design.This article is part of the themed issue 'Membrane pores: from structure and assembly, to medicine and technology'.


Assuntos
Proteínas de Membrana/química , Engenharia de Proteínas , Conformação Proteica em alfa-Hélice
12.
Bioinformatics ; 33(19): 3043-3050, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28582565

RESUMO

MOTIVATION: The rational design of biomolecules is becoming a reality. However, further computational tools are needed to facilitate and accelerate this, and to make it accessible to more users. RESULTS: Here we introduce ISAMBARD, a tool for structural analysis, model building and rational design of biomolecules. ISAMBARD is open-source, modular, computationally scalable and intuitive to use. These features allow non-experts to explore biomolecular design in silico. ISAMBARD addresses a standing issue in protein design, namely, how to introduce backbone variability in a controlled manner. This is achieved through the generalization of tools for parametric modelling, describing the overall shape of proteins geometrically, and without input from experimentally determined structures. This will allow backbone conformations for entire folds and assemblies not observed in nature to be generated de novo, that is, to access the 'dark matter of protein-fold space'. We anticipate that ISAMBARD will find broad applications in biomolecular design, biotechnology and synthetic biology. AVAILABILITY AND IMPLEMENTATION: A current stable build can be downloaded from the python package index (https://pypi.python.org/pypi/isambard/) with development builds available on GitHub (https://github.com/woolfson-group/) along with documentation, tutorial material and all the scripts used to generate the data described in this paper. CONTACT: d.n.woolfson@bristol.ac.uk or chris.wood@bristol.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Conformação Proteica , Software , Simulação por Computador , Modelos Moleculares , Dobramento de Proteína , Proteínas/química
13.
Nat Chem ; 9(5): 411-419, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28430192

RESUMO

The fabrication of monodisperse transmembrane barrels formed from short synthetic peptides has not been demonstrated previously. This is in part because of the complexity of the interactions between peptides and lipids within the hydrophobic environment of a membrane. Here we report the formation of a transmembrane pore through the self-assembly of 35 amino acid α-helical peptides. The design of the peptides is based on the C-terminal D4 domain of the Escherichia coli polysaccharide transporter Wza. By using single-channel current recording, we define discrete assembly intermediates and show that the pore is most probably a helix barrel that contains eight D4 peptides arranged in parallel. We also show that the peptide pore is functional and capable of conducting ions and binding blockers. Such α-helix barrels engineered from peptides could find applications in nanopore technologies such as single-molecule sensing and nucleic-acid sequencing.


Assuntos
Materiais Biomiméticos/metabolismo , Canais Iônicos/metabolismo , Bicamadas Lipídicas/metabolismo , Oligopeptídeos/metabolismo , Sequência de Aminoácidos , Proteínas da Membrana Bacteriana Externa/química , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Ciclodextrinas/química , Cisteína/química , Escherichia coli/química , Proteínas de Escherichia coli/química , Canais Iônicos/síntese química , Canais Iônicos/química , Bicamadas Lipídicas/química , Simulação de Dinâmica Molecular , Nanoporos , Oligopeptídeos/síntese química , Oligopeptídeos/química , Fosfatidilcolinas/química , Conformação Proteica em alfa-Hélice , Engenharia de Proteínas , Subunidades Proteicas/síntese química , Subunidades Proteicas/química , Subunidades Proteicas/metabolismo
14.
ACS Synth Biol ; 6(6): 1096-1102, 2017 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-28221767

RESUMO

Improving our understanding of biological motors, both to fully comprehend their activities in vital processes, and to exploit their impressive abilities for use in bionanotechnology, is highly desirable. One means of understanding these systems is through the production of synthetic molecular motors. We demonstrate the use of orthogonal coiled-coil dimers (including both parallel and antiparallel coiled coils) as a hub for linking other components of a previously described synthetic molecular motor, the Tumbleweed. We use circular dichroism, analytical ultracentrifugation, dynamic light scattering, and disulfide rearrangement studies to demonstrate the ability of this six-peptide set to form the structure designed for the Tumbleweed motor. The successful formation of a suitable hub structure is both a test of the transferability of design rules for protein folding as well as an important step in the production of a synthetic protein-based molecular motor.


Assuntos
Proteínas Motores Moleculares/química , Engenharia de Proteínas/métodos , Subunidades Proteicas/química , Biologia Sintética/métodos , Dicroísmo Circular , Modelos Moleculares , Proteínas Motores Moleculares/metabolismo , Peptídeos/química , Peptídeos/metabolismo , Multimerização Proteica , Estrutura Secundária de Proteína , Subunidades Proteicas/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
15.
Nat Chem ; 8(9): 837-44, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27554410

RESUMO

The design of enzyme-like catalysts tests our understanding of sequence-to-structure/function relationships in proteins. Here we install hydrolytic activity predictably into a completely de novo and thermostable α-helical barrel, which comprises seven helices arranged around an accessible channel. We show that the lumen of the barrel accepts 21 mutations to functional polar residues. The resulting variant, which has cysteine-histidine-glutamic acid triads on each helix, hydrolyses p-nitrophenyl acetate with catalytic efficiencies that match the most-efficient redesigned hydrolases based on natural protein scaffolds. This is the first report of a functional catalytic triad engineered into a de novo protein framework. The flexibility of our system also allows the facile incorporation of unnatural side chains to improve activity and probe the catalytic mechanism. Such a predictable and robust construction of truly de novo biocatalysts holds promise for applications in chemical and biochemical synthesis.


Assuntos
Hidrolases de Éster Carboxílico/química , Engenharia de Proteínas , Hidrolases de Éster Carboxílico/genética , Catálise , Domínio Catalítico , Hidrólise , Cinética , Mutação , Nitrofenóis/química , Conformação Proteica em alfa-Hélice , Engenharia de Proteínas/métodos , Estrutura Terciária de Proteína
16.
Nature ; 529(7584): 76-9, 2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26738593

RESUMO

Interactions between crustal and mantle reservoirs dominate the surface inventory of volatile elements over geological time, moderating atmospheric composition and maintaining a life-supporting planet. While volcanoes expel volatile components into surface reservoirs, subduction of oceanic crust is responsible for replenishment of mantle reservoirs. Many natural, 'superdeep' diamonds originating in the deep upper mantle and transition zone host mineral inclusions, indicating an affinity to subducted oceanic crust. Here we show that the majority of slab geotherms will intersect a deep depression along the melting curve of carbonated oceanic crust at depths of approximately 300 to 700 kilometres, creating a barrier to direct carbonate recycling into the deep mantle. Low-degree partial melts are alkaline carbonatites that are highly reactive with reduced ambient mantle, producing diamond. Many inclusions in superdeep diamonds are best explained by carbonate melt-peridotite reaction. A deep carbon barrier may dominate the recycling of carbon in the mantle and contribute to chemical and isotopic heterogeneity of the mantle reservoir.

17.
Angew Chem Int Ed Engl ; 55(3): 987-91, 2016 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-26663438

RESUMO

An ability to control the assembly of peptide nanotubes (PNTs) would provide biomaterials for applications in nanotechnology and synthetic biology. Recently, we presented a modular design for PNTs using α-helical barrels with tunable internal cavities as building blocks. These first-generation designs thicken beyond single PNTs. Herein we describe strategies for controlling this lateral association, and also for the longitudinal assembly. We show that PNT thickening is pH sensitive, and can be reversed under acidic conditions. Based on this, repulsive charge interactions are engineered into the building blocks leading to the assembly of single PNTs at neutral pH. The building blocks are modified further to produce covalently linked PNTs via native chemical ligation, rendering ca. 100 nm-long nanotubes. Finally, we show that small molecules can be sequestered within the interior lumens of single PNTs.


Assuntos
Nanotubos de Peptídeos/química , Microscopia Eletrônica de Transmissão , Conformação Proteica
18.
J Appl Crystallogr ; 48(Pt 6): 1914-1920, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26664346

RESUMO

The equation of state of the orthorhombic phase of NiSi with Pmmn symmetry has been determined at room temperature from synchrotron-based X-ray diffraction measurements of its lattice parameters, made in a diamond anvil cell. Measurements were performed up to 44 GPa, using Ne as the pressure medium and Au as the pressure standard. The resulting pressure-volume (P-V) data have been fitted with a Birch-Murnaghan equation of state of third order to yield V0 = 11.650 (7) Å3 atom-1, K0 = 162 (3) GPa and K0' = 4.6 (2). In addition, P-V data have been collected on Ni53Si47 in the B20 structure using both Ne and He as the pressure media and Cu and Au as the pressure standards, also to 44 GPa. A fit using the same Birch-Murnaghan equation of state of third order yields V0 = 11.364 (6) Å3 atom-1, K0 = 171 (4) GPa and K0' = 5.5 (3).

19.
ACS Biomater Sci Eng ; 1(6): 431-439, 2015 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-26240838

RESUMO

Trauma to the central and peripheral nervous systems often lead to serious morbidity. Current surgical methods for repairing or replacing such damage have limitations. Tissue engineering offers a potential alternative. Here we show that functionalized α-helical-peptide hydrogels can be used to induce attachment, migration, proliferation and differentiation of murine embryonic neural stem cells (NSCs). Specifically, compared with undecorated gels, those functionalized with Arg-Gly-Asp-Ser (RGDS) peptides increase the proliferative activity of NSCs; promote their directional migration; induce differentiation, with increased expression of microtubule-associated protein-2, and a low expression of glial fibrillary acidic protein; and lead to the formation of larger neurospheres. Electrophysiological measurements from NSCs grown in RGDS-decorated gels indicate developmental progress toward mature neuron-like behavior. Our data indicate that these functional peptide hydrogels may go some way toward overcoming the limitations of current approaches to nerve-tissue repair.

20.
J Am Chem Soc ; 137(33): 10554-62, 2015 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-26219086

RESUMO

An ability to design peptide-based nanotubes (PNTs) rationally with defined and mutable internal channels would advance understanding of peptide self-assembly, and present new biomaterials for nanotechnology and medicine. PNTs have been made from Fmoc dipeptides, cyclic peptides, and lock-washer helical bundles. Here we show that blunt-ended α-helical barrels, that is, preassembled bundles of α-helices with central channels, can be used as building blocks for PNTs. This approach is general and systematic, and uses a set of de novo helical bundles as standards. One of these bundles, a hexameric α-helical barrel, assembles into highly ordered PNTs, for which we have determined a structure by combining cryo-transmission electron microscopy, X-ray fiber diffraction, and model building. The structure reveals that the overall symmetry of the peptide module plays a critical role in ripening and ordering of the supramolecular assembly. PNTs based on pentameric, hexameric, and heptameric α-helical barrels sequester hydrophobic dye within their lumens.


Assuntos
Nanotecnologia/métodos , Nanotubos de Peptídeos/química , Sequência de Aminoácidos , Modelos Moleculares , Dados de Sequência Molecular , Polimerização , Estrutura Secundária de Proteína , Desdobramento de Proteína , Temperatura
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