RESUMO
Proton-coupled electron transfer (PCET) is key to the activation of the blue light using flavin (BLUF) domain photoreceptors. Here, to elucidate the photocycle of the central FMN-Gln-Tyr motif in the BLUF domain of OaPAC, we eliminated the intrinsic interfering W90 in the mutant design. We integrated the stretched exponential function into the target analysis to account for the dynamic heterogeneity arising from the active-site solvation relaxation and the flexible H-bonding network as shown in the molecular dynamics simulation results, facilitating a simplified expression of the kinetics model. We find that, in both the functional wild-type (WT) and the nonfunctional Q48E and Q48A, forward PCET happens in the range of 105 ps to 344 ps, with a kinetic isotope effect (KIE) measured to be â¼1.8 to 2.4, suggesting that the nature of the forward PCET is concerted. Remarkably, only WT proceeds with an ultrafast reverse PCET process (31 ps, KIE = 4.0), characterized by an inverted kinetics of the intermediate FMNHË. Our results reveal that the reverse PCET is driven by proton transfer via an intervening imidic Gln.
Assuntos
Transporte de Elétrons , Flavinas , Luz , Flavinas/genética , Flavinas/metabolismo , Simulação de Dinâmica Molecular , PrótonsRESUMO
Controlling the enantioselectivity of hydrogen atom transfer (HAT) reactions has been a long-standing synthetic challenge. While recent advances on photoenzymatic catalysis have demonstrated the great potential of non-natural photoenzymes, all of the transformations are initiated by single-electron reduction of the substrate, with only one notable exception. Herein, we report an oxidation-initiated photoenzymatic enantioselective hydrosulfonylation of olefins using a novel mutant of gluconobacter ene-reductase (GluER-W100F-W342F). Compared to known photoenzymatic systems, our approach does not rely on the formation of an electron donor-acceptor complex between the substrates and enzyme cofactor and simplifies the reaction system by obviating the addition of a cofactor regeneration mixture. More importantly, the GluER variant exhibits high reactivity and enantioselectivity and a broad substrate scope. Mechanistic studies support the proposed oxidation-initiated mechanism and reveal that a tyrosine-mediated HAT process is involved.
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Alcenos , Elétrons , Estereoisomerismo , Oxirredução , Hidrogênio , CatáliseRESUMO
Remote patient-monitoring systems are helpful since they can provide timely and effective healthcare facilities. Such online telemedicine is usually achieved with the help of sophisticated and advanced wearable sensor technologies. The modern type of wearable connected devices enable the monitoring of vital sign parameters such as: heart rate variability (HRV) also known as electrocardiogram (ECG), blood pressure (BLP), Respiratory rate and body temperature, blood pressure (BLP), respiratory rate, and body temperature. The ubiquitous problem of wearable devices is their power demand for signal transmission; such devices require frequent battery charging, which causes serious limitations to the continuous monitoring of vital data. To overcome this, the current study provides a primary report on collecting kinetic energy from daily human activities for monitoring vital human signs. The harvested energy is used to sustain the battery autonomy of wearable devices, which allows for a longer monitoring time of vital data. This study proposes a novel type of stress- or exercise-monitoring ECG device based on a microcontroller (PIC18F4550) and a Wi-Fi device (ESP8266), which is cost-effective and enables real-time monitoring of heart rate in the cloud during normal daily activities. In order to achieve both portability and maximum power, the harvester has a small structure and low friction. Neodymium magnets were chosen for their high magnetic strength, versatility, and compact size. Due to the non-linear magnetic force interaction of the magnets, the non-linear part of the dynamic equation has an inverse quadratic form. Electromechanical damping is considered in this study, and the quadratic non-linearity is approximated using MacLaurin expansion, which enables us to find the law of motion for general case studies using classical methods for dynamic equations and the suitable parameters for the harvester. The oscillations are enabled by applying an initial force, and there is a loss of energy due to the electromechanical damping. A typical numerical application is computed with Matlab 2015 software, and an ODE45 solver is used to verify the accuracy of the method.
Assuntos
Eletrocardiografia , Frequência Cardíaca , Dispositivos Eletrônicos Vestíveis , Frequência Cardíaca/fisiologia , Humanos , Monitorização Fisiológica/instrumentação , Monitorização Fisiológica/métodos , Eletrocardiografia/métodos , Eletrocardiografia/instrumentação , Fontes de Energia Elétrica , Internet das Coisas , Cinética , Telemedicina/instrumentaçãoRESUMO
In the field of biocatalysis, discovering novel reactivity from known enzymes has been a longstanding challenge. Fatty acid photo-decarboxylase from Chlorella variabilis (CvFAP) has drawn considerable attention as a promising photoenzyme with potential green chemistry applications; however, its non-natural reactivity has rarely been exploited to date. Herein we report a non-natural reductive dehalogenation (deacetoxylation) reactivity of CvFAP inspired by its natural oxidative decarboxylation process, enabling the stereoselective synthesis of a series of chiral α-substituted tetralones with high yields (up to 99%) and e.r. values (up to 99:1). Mechanistic studies demonstrated that the native photoenzyme catalyzed the reductive dehalogenation via a novel mechanism involving oxidized state (FADox) / semiquinone state (FADsq) redox pair and an electron transfer (ET)/proton transfer (PT) process of radical termination, distinct from the previous reports. To our knowledge, this study represents a new example of CvFAP promiscuity, and thus expands the reactivity repertoire of CvFAP and highlights the versatility of CvFAP in asymmetric synthesis.
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Proton relays through H-bond networks are essential in realizing the functionality of protein machines such as in photosynthesis and photoreceptors. It has been challenging to dissect the rates and energetics of individual proton-transfer steps during the proton relay. Here, we have designed a proton rocking blue light using a flavin (BLUF) domain with the flavin mononucleotide (FMN)-glutamic acid (E)-tryptophan (W) triad and have resolved the four individual proton-transfer steps kinetically using ultrafast spectroscopy. We have found that after the photo-induced charge separation forming FMN·-/E-COOH/WH·+, the proton first rapidly jumps from the bridging E-COOH to FMN- (τfPT2 = 3.8 ps; KIE = 1.0), followed by a second proton transfer from WH·+ to E-COO- (τfPT1 = 336 ps; KIE = 2.6) which immediately rocks back to W· (τrPT1 = 85 ps; KIE = 6.7), followed by a proton return from FMNH· to E-COO- (τrPT2 = 34 ps; KIE = 3.3) with the final charge recombination between FMN·- and WH·+ to close the reaction cycle. Our results revisited the Grotthuss mechanism on the ultrafast timescale using the BLUF domain as a paradigm protein.
Assuntos
Luz , Prótons , Análise Espectral , TriptofanoRESUMO
Phototriggers are useful molecular tools to initiate reactions in enzymes by light for the purpose of photoenzymatic design and mechanistic investigations. Here, we incorporated the non-natural amino acid 5-cyanotryptophan (W5CN) in a polypeptide scaffold and resolved the photochemical reaction of the W5CN-W motif using femtosecond transient UV/Vis and mid-IR spectroscopy. We identified a marker band of â¼2037 cm-1 from the CN stretch of the electron transfer intermediate W5CN·- in the transient IR measurement and found UV/Vis spectroscopic evidence for the W·+ radical at 580 nm. Through kinetic analysis, we characterized that the charge separation between the excited W5CN and W occurs in 253 ps, with a charge-recombination lifetime of 862 ps. Our study highlights the potential use of the W5CN-W pair as an ultrafast phototrigger to initiate reactions in enzymes that are not light-sensitive, making downstream reactions accessible to femtosecond spectroscopic detection.
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Cinética , Transporte de ElétronsRESUMO
Self-powered biomedical devices, which are the new vision of Internet Of Things (IOT) healthcare, are facing many technical and application challenges. Many research works have reported biomedical devices and self-powered applications for healthcare, along with various strategies to improve the monitoring time of self-powered devices or to eliminate the dependence on electrochemical batteries. However, none of these works have especially assessed the development and application of healthcare devices in an African context. This article provides a comprehensive review of self-powered devices in the biomedical research field, introduces their applications for healthcare, evaluates their status in Africa by providing a thorough review of existing biomedical device initiatives and available financial and scientific cooperation institutions in Africa for the biomedical research field, and highlights general challenges for implementing self-powered biomedical devices and particular challenges related to developing countries. The future perspectives of the aforementioned research field are provided, as well as an architecture for improving this research field in developing countries.
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Pesquisa Biomédica , Fenômenos Físicos , África , Fontes de Energia Elétrica , CabeçaRESUMO
Native chemical ligation (NCL) provides a powerful solution to assemble proteins with precise chemical features, which enables a detailed investigation of the protein structure-function relationship. As an extension to NCL, the discovery of desulfurization and expressed protein ligation (EPL) techniques has greatly expanded the efficient access to large or challenging protein sequences via chemical ligations. Despite its superior reliability, the NCL-desulfurization protocol requires orthogonal protection strategies to allow selective desulfurization in the presence of native Cys, which is crucial to its synthetic application. In contrast to traditional thiol protecting groups, photolabile protecting groups (PPGs), which are removed upon irradiation, simplify protein assembly and therefore provide minimal perturbation to the peptide scaffold. However, current PPG strategies are mainly limited to nitro-benzyl derivatives, which are incompatible with NCL-desulfurization. Herein, we present for the first time that quinoline-based PPG for cysteine can facilitate various ligation strategies, including iterative NCL and EPL-desulfurization methods. 7-(Piperazin-1-yl)-2-(methyl)quinolinyl (PPZQ) caging of multiple cysteine residues within the protein sequence can be readily introduced via late-stage modification, while the traceless removal of PPZQ is highly efficient via photolysis in an aqueous buffer. In addition, the PPZQ group is compatible with radical desulfurization. The efficiency of this strategy has been highlighted by the synthesis of γ-synuclein and phosphorylated cystatin-S via one-pot iterative ligation and EPL-desulfurization methods. Besides, successful sextuple protection and deprotection of the expressed Interleukin-34 fragment demonstrate the great potential of this strategy in protein caging/uncaging investigations.
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ProteínasRESUMO
We present direct observation of ultrafast proton rocking in the central motif of a BLUF domain protein scaffold. The mutant design has taken consideration of modulating the proton-coupled electron transfer (PCET) driving forces by replacing Tyr in the original motif with Trp, in order to remove the interference of a competing electron transfer pathway. Using femtosecond pump-probe spectroscopy and detailed kinetics analysis, we resolved an electron-transfer-coupled Grotthuss-type forward and reverse proton rocking along the FMN-Gln-Trp proton relay chain. The rates of forward and reverse proton transfer are determined to be very close, namely 51â ps vs. 52â ps. The kinetic isotope effect (KIE) constants associated with the forward and reverse proton transfer are 3.9 and 5.3, respectively. The observation of ultrafast proton rocking is not only a crucial step towards revealing the nature of proton relay in the BLUF domain, but also provides a new paradigm of proton transfer in proteins for theoretical investigations.
Assuntos
Adenilil Ciclases/química , Flavina-Adenina Dinucleotídeo/química , Luz , Prótons , Adenilil Ciclases/metabolismo , Transporte de Elétrons , Flavina-Adenina Dinucleotídeo/metabolismo , Oscillatoria/enzimologia , Domínios ProteicosRESUMO
Short-range protein electron transfer (ET) is ubiquitous in biology and is often observed in photosynthesis, photoreceptors and photoenzymes. These ET processes occur on an ultrafast timescale from femtoseconds to picoseconds at a short donor-acceptor distance within 10 Å, and thus couple with local environmental fluctuations. Here, we use oxidized Anabaena flavodoxin as a model system and have systematically studied the photoinduced redox cycle of the wild type and seven mutant proteins by femtosecond spectroscopy. We observed a series of ultrafast dynamics from the initial charge separation in 100-200 fs, subsequent charge recombination in 1-2 ps and final vibrational cooling process of the products in 3-6 ps. We further characterized the active-site solvation and observed the relaxations in 1-200 ps, indicating a nonergodic ET dynamics. With our new ET model, we uncovered a minor outer (solvent) reorganization energy and a large inner (donor and acceptor) reorganization energy, suggesting a frozen active site in the initial ultrafast ET while the back ET couples with the environment relaxations. The vibronically coupled back ET dynamics was first reported in D. vulgaris flavodoxin and here is observed in Anabaena flavodoxin again, completely due to the faster ET dynamics than the cooling relaxations. We also compared the two flavodoxin structures, revealing a stronger coupling with the donor tyrosine in Anabaena. All ultrafast ET dynamics are from the large donor-acceptor couplings and the minor activation barriers due to the reaction free energies being close to the inner reorganization energies. These observations should be general to many redox reactions in flavoproteins.
Assuntos
Flavodoxina/metabolismo , Simulação de Dinâmica Molecular , Proteínas/metabolismo , Anabaena/química , Anabaena/metabolismo , Transporte de Elétrons , Flavodoxina/química , Proteínas/químicaRESUMO
Two-dimensional (2D) van der Waals (vdW) magnetic materials have recently been introduced as a new horizon in materials science, and they enable potential applications for next-generation spintronic devices. Here, in this communication, the observations of stable Bloch-type magnetic skyrmions in single crystals of 2D vdW Fe3GeTe2 (FGT) are reported by using in situ Lorentz transmission electron microscopy (TEM). We find the ground-state magnetic stripe domains in FGT transform into skyrmion bubbles when an external magnetic field is applied perpendicularly to the (001) thin plate with temperatures below the Curie temperature TC. Most interestingly, a hexagonal lattice of skyrmion bubbles is obtained via field-cooling manipulation with magnetic field applied along the [001] direction. Owing to their topological stability, the skyrmion bubble lattices are stable to large field-cooling tilted angles and further reproduced by utilizing the micromagnetic simulations. These observations directly demonstrate that the 2D vdW FGT possesses a rich variety of topological spin textures, being of great promise for future applications in the field of spintronics.
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Many ions are known to affect the activity, stability, and structural integrity of proteins. Although this effect can be generally attributed to ion-induced changes in forces that govern protein folding, delineating the underlying mechanism of action still remains challenging because it requires assessment of all relevant interactions, such as ion-protein, ion-water, and ion-ion interactions. Herein, we use two unnatural aromatic amino acids and several spectroscopic techniques to examine whether guanidinium chloride, one of the most commonly used protein denaturants, and tetrapropylammonium chloride can specifically interact with aromatic side chains. Our results show that tetrapropylammonium, but not guanidinium, can preferentially accumulate around aromatic residues and that tetrapropylammonium undergoes a transition at â¼1.3 M to form aggregates. We find that similar to ionic micelles, on one hand, such aggregates can disrupt native hydrophobic interactions, and on the other hand, they can promote α-helix formation in certain peptides.
Assuntos
Alanina/análogos & derivados , Aminoácidos Aromáticos/efeitos dos fármacos , Guanidina/farmacologia , Compostos de Amônio Quaternário/farmacologia , Espectrofotometria Infravermelho/métodos , Alanina/química , Alanina/efeitos dos fármacos , Aminoácidos Aromáticos/química , Peptídeos Catiônicos Antimicrobianos/química , Dicroísmo Circular , Guanidina/química , Interações Hidrofóbicas e Hidrofílicas , Nitrilas/química , Peptídeos/química , Desnaturação Proteica , Estabilidade Proteica/efeitos dos fármacos , Estrutura Secundária de Proteína/efeitos dos fármacos , Compostos de Amônio Quaternário/química , Solventes , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
INTRODUCTION: White matter hyperintensities (WMHs) were commonly seen in brain magnetic resonance imaging (MRI) of the elderly. Many studies found that WMHs were associated with cognitive decline and dementia. However, the association between WMHs in different brain regions and cognitive decline remains debated. METHODS: We explored the association of the severity of WMHs and cognitive decline in 115 non-demented elderly (≥50 years old) sampled from the Wuliqiao Community located in urban area of Shanghai. MRI scans were done during 2009-2011 at the beginning of the study. Severity of WMHs in different brain regions was scored by Improved Scheltens Scale and Cholinergic Pathways Hyperintensities Scale (CHIPS). Cognitive function was evaluated by Mini-Mental State Examination (MMSE) every 2 to 4 years during 2009-2018. RESULTS: After adjusting for confounding factors including age, gender, education level, smoking status, alcohol consumption, depression, hypertension, diabetes, hyperlipidemia, brain infarcts, brain atrophy, apoE4 status, and baseline MMSE score, periventricular and subcortical WMH lesions as well as WMHs in cholinergic pathways were significantly associated with annual MMSE decline ( p < 0.05), in which the severity of periventricular WMHs predicted a faster MMSE decline (-0.187 points/year, 95% confidence interval: -0.349, -0.026, p = 0.024). CONCLUSIONS: The severity of WMHs at baseline was associated with cognitive decline in the non-demented elderly over time. Interventions on WMH lesions may offer some benefits for cognitive deterioration.
Des hyper-signaux de la substance blanche prédicteurs du déclin cognitif : une étude menée dans une communauté locale.Introduction: Des hyper-signaux de la substance blanche (HSSB) peuvent généralement être observés lors d'examens d'imagerie par résonnance magnétique (IRM) effectués chez des personnes âgées. Plusieurs études ont également montré que les HSSB étaient associés au déclin cognitif et à la démence. Cela dit, le lien pouvant exister entre ces HSSB détectés dans diverses régions cérébrales et le déclin cognitif demeure sujet à débat. Méthodes: Nous avons décidé d'explorer l'association existant entre l'intensité des HSSB et le déclin cognitif chez 115 personnes âgées n'étant pas atteintes de démence (≥50 ans). Ces personnes avaient été recrutées au sein du quartier de Wuliqiao situé dans le grand Shanghai. Signalons que ces examens d'IRM ont été effectués au début de cette étude entre 2009 et 2011. L'intensité des HSSB dans diverses régions cérébrales a été mesurée au moyen des échelles suivantes : la Improved Scheltens Scale et la Cholinergic Pathways Hyperintensities Scale (CHIPS). En ce qui concerne la fonction cognitive, elle a été évaluée à l'aide du test de Folstein (ou mini-mental state examination) tous les 2 à 4 ans entre 2009 et 2018. Résultats: Une fois la prise en compte d'un certain nombre de facteurs de confusion (l'âge, le sexe, le niveau de scolarité, le tabagisme, la consommation d'alcool, la dépression, l'hypertension, le diabète, l'hyperlipidémie, des accidents ischémiques cérébraux, une atrophie du cerveau, la situation de l'allèle 4 du gène ApoE et le score initial au test de Folstein), il est apparu que des lésions révélées par des hyper-signaux des régions péri-ventriculaire et sous-corticale, de même que des hyper-signaux détectés dans les voies cholinergiques, étaient nettement associés à des résultats en baisse au test de Folstein en cours d'année (p < 0,05). Fait à noter, l'intensité des HSSB de la région péri-ventriculaire a aussi permis de prédire un déclin plus rapide des scores au test de Folstein (- 0,187 points/année, IC 95 % : - 0,349 - 0,026; p = 0,024). Conclusions: L'intensité des HSSB observée au début de cette étude a été associée au fil du temps au déclin cognitif de personnes âgées n'étant pas atteintes de démence. Il est donc possible que des interventions ciblant des lésions révélées par des HSSB puissent offrir certains bienfaits quand il est question de déclin cognitif.
Assuntos
Encéfalo/patologia , Disfunção Cognitiva/patologia , Substância Branca/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-IdadeRESUMO
Nanoscale topologically nontrivial spin textures, such as magnetic skyrmions, have been identified as promising candidates for the transport and storage of information for spintronic applications, notably magnetic racetrack memory devices. The design and realization of a single skyrmion chain at room temperature (RT) and above in the low-dimensional nanostructures are of great importance for future practical applications. Here, we report the creation of a single skyrmion bubble chain in a geometrically confined Fe3Sn2 nanostripe with a width comparable to the featured size of a skyrmion bubble. Systematic investigations on the thermal stability have revealed that the single chain of skyrmion bubbles can keep stable at temperatures varying from RT up to a record-high temperature of 630 K. This extreme stability can be ascribed to the weak temperature-dependent magnetic anisotropy and the formation of edge states at the boundaries of the nanostripes. The realization of the highly stable skyrmion bubble chain in a geometrically confined nanostructure is a very important step toward the application of skyrmion-based spintronic devices.
Assuntos
Eletrocardiografia , Síncope , Pré-Escolar , Diagnóstico Diferencial , Humanos , Síncope/diagnóstico , Síncope/etiologiaRESUMO
Herein, we combine several methods to characterize the fibrils formed by a TTR105-115 mutant in which Leu111 is replaced by the unnatural amino acid aspartic acid 4-methyl ester. We find that this mutant peptide exhibits significantly different aggregation behavior than the wild-type peptide: (1) it forms fibrils with a much faster rate, (2) its fibrils lack the long-range helical twists observed in TTR105-115 fibrils, (3) its fibrils exhibit a giant far-UV circular dichroism signal, and (4) its fibrils give rise to an unusual amide I' band consisting of four distinct and sharp peaks. On the basis of these results and also several previous computational studies, we hypothesize that the fibrils formed by this TTR mutant peptide contain both ß- and α-sheets.
Assuntos
Peptídeos beta-Amiloides/genética , Amiloide/genética , Amiloide/química , Peptídeos beta-Amiloides/química , Mutação , Multimerização Proteica/genética , Estrutura Secundária de ProteínaRESUMO
We demonstrate surfactant- and template-free synthesis of superhydrophobic thin films by controlling surface morphology. The surface morphology evolution process was determined from time-dependent studies. The relationships between the water contact angle, sliding angle, water droplet size, and surface microstructures were investigated. It is found that structural parameters play an important role in determining the adhesion of a droplet on superhydrophobic surfaces and the liquid-solid adhesion can be effectively manipulated through tailoring the morphology or the size of the microstructures on the surface. We provide a theoretical explanation for the Cassie-Baxter state (water rolls) and the Wenzel state (sticky surface, water adheres) with droplet size on different microstructure surfaces. The new theoretical insight provided in this study matches well with experimental results.
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Magnetic skyrmions, particular those without the support of external magnetic fields over a wide temperature region, are promising as alternative spintronic units to overcome the fundamental size limitation of conventional magnetic bits. In this study, we use in situ Lorentz microscope to directly demonstrate the generation and sustainability of robust biskyrmion lattice at zero magnetic field over a wide temperature range of 16-338 K in MnNiGa alloy. This procedure includes a simple field-cooling manipulation from 360 K (higher than Curie temperature TC â¼ 350 K), where topological transition easily occurs by adapting the short-range magnetic clusters under a certain magnetic field. The biskyrmion phase is favored upon cooling below TC. Once they are generated, the robust high-density biskyrmions persist even after removing the external magnetic field due to the topological protection and the increased energy barrier.
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Understanding molecular structures of interfacial peptides and proteins impacts many research fields by guiding the advancement of biocompatible materials, new and improved marine antifouling coatings, ultrasensitive and highly specific biosensors and biochips, therapies for diseases related to protein amyloid formation, and knowledge on mechanisms for various membrane proteins and their interactions with ligands. Developing methods for measuring such unique systems, as well as elucidating the structure and function relationship of such biomolecules, has been the goal of our lab at the University of Michigan. We have made substantial progress to develop sum frequency generation (SFG) vibrational spectroscopy into a powerful technique to study interfacial peptides and proteins, which lays a foundation to obtain unique and valuable insights when using SFG to probe various biologically relevant systems at the solid/liquid interface in situ in real time. One highlighting feature of this Account is the demonstration of the power of combining SFG with other techniques and methods such as ATR-FTIR, surface engineering, MD simulation, liquid crystal sensing, and isotope labeling in order to study peptides and proteins at interfaces. It is necessary to emphasize that SFG plays a major role in these studies, while other techniques and methods are supplemental. The central role of SFG is to provide critical information on interfacial peptide and protein structure (e.g., conformation and orientation) in order to elucidate how surface engineering (e.g., to vary the structure) can ultimately affect surface function (e.g., to optimize the activity). This Account focuses on the most significant recent progress in research on interfacial peptides and proteins carried out by our group including (1) the development of SFG analysis methods to determine orientations of regular as well as disrupted secondary structures, and the successful demonstration and application of an isotope labeling method with SFG to probe the detailed local structure and microenvironment of peptides at buried interfaces, (2) systematic research on cell membrane associated peptides and proteins including antimicrobial peptides, cell penetrating peptides, G proteins, and other membrane proteins, discussing the factors that influence interfacial peptide and protein structures such as lipid charge, membrane fluidity, and biomolecule solution concentration, and (3) in-depth discussion on solid surface immobilized antimicrobial peptides and enzymes. The effects of immobilization method, substrate surface, immobilization site on the peptide or protein, and surrounding environment are presented. Several examples leading to high impact new research are also briefly introduced: The orientation change of alamethicin detected while varying the model cell membrane potential demonstrates the feasibility to apply SFG to study ion channel protein gating mechanisms. The elucidation of peptide secondary structures at liquid crystal interfaces shows promising results that liquid crystal can detect and recognize different peptides and proteins. The method of retaining the native structure of surface immobilized peptides or proteins in air demonstrates the feasibility to protect and preserve such structures via the use of hydromimetic functionalities when there is no bulk water. We hope that readers in many different disciplines will benefit from the research progress reported in this Account on SFG studies of interfacial structure-function relationships of peptides and proteins and apply this powerful technique to study interfacial biomolecules in the future.
Assuntos
Peptídeos/química , Engenharia de Proteínas , Proteínas/química , Análise Espectral/métodos , Membrana Celular , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , VibraçãoRESUMO
Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron-rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor-dominant PD patients using quantitative susceptibility mapping. Forty-three patients with PD [19 tremor dominant (TD)/24 akinetic rigidity (AR) dominant] and 48 healthy gender- and age-matched controls were recruited. Multi-echo gradient echo data were collected for each subject on a 3.0-T MR system. Inter-group susceptibility differences in the bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast with the AR-dominant group, the TD group was found to have increased susceptibility in the bilateral DN when compared with healthy controls. In addition, susceptibility was positively correlated with tremor score in drug-naive PD patients. These findings indicate that iron load within the DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR-dominant phenotypes of PD can be differentiated on the basis of the susceptibility of the DN, at least at the group level. Copyright © 2016 John Wiley & Sons, Ltd.