Journal of structural biology最新文献_第9页

Structural analysis of the water channel AQP2 by single-particle cryo-EM 水通道AQP2的单颗粒低温电镜结构分析

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.107984

Akiko Kamegawa , Shota Suzuki , Hiroshi Suzuki , Kouki Nishikawa , Nobutaka Numoto , Yoshinori Fujiyoshi

{"title":"Structural analysis of the water channel AQP2 by single-particle cryo-EM","authors":"Akiko Kamegawa , Shota Suzuki , Hiroshi Suzuki , Kouki Nishikawa , Nobutaka Numoto , Yoshinori Fujiyoshi","doi":"10.1016/j.jsb.2023.107984","DOIUrl":"10.1016/j.jsb.2023.107984","url":null,"abstract":"<div><p>Water channels, which are small membrane proteins almost entirely buried in lipid membranes, are challenging research targets for single-particle cryo-electron microscopy (cryo-EM), a powerful technique routinely used to determine the structures of membrane proteins. Because the single-particle method enables structural analysis of a whole protein with flexible parts that interfere with crystallization, we have focused our efforts on analyzing water channel structures. Here, utilizing this system, we analyzed the structure of full-length aquaporin-2 (AQP2), a primary regulator of vasopressin-dependent reabsorption of water at the renal collecting ducts. The 2.9 Å resolution map revealed a cytoplasmic extension of the cryo-EM density that was presumed to be the highly flexible C-terminus at which the localization of AQP2 is regulated in the renal collecting duct cells. We also observed a continuous density along the common water pathway inside the channel pore and lipid-like molecules at the membrane interface. Observations of these constructions in the AQP2 structure analyzed without any fiducial markers (e.g., a rigidly bound antibody) indicate that single-particle cryo-EM will be useful for investigating water channels in native states as well as in complexes with chemical compounds.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10220161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unusual structural and functional features of TpLRR/BspA-like LRR proteins TpLRR/ bspa样LRR蛋白的异常结构和功能特征

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.108011

Abraham Takkouche , Xinru Qiu , Mayya Sedova , Lukasz Jaroszewski , Adam Godzik

{"title":"Unusual structural and functional features of TpLRR/BspA-like LRR proteins","authors":"Abraham Takkouche , Xinru Qiu , Mayya Sedova , Lukasz Jaroszewski , Adam Godzik","doi":"10.1016/j.jsb.2023.108011","DOIUrl":"10.1016/j.jsb.2023.108011","url":null,"abstract":"<div><p>Leucine Rich Repeat (LRR) domains, are present in hundreds of thousands of proteins across all kingdoms of life and are typically involved in protein–protein interactions and ligand recognition. LRR domains are classified into eight classes and when examined in three dimensions seven, of them form curved solenoid-like super-helices, also described as toruses, with a beta sheet on the concave (inside) and stacked alpha-helices on the convex (outside) of the torus. Here we present an overview of the least characterized 8th class of LRR proteins, the TpLRR-like LRRs, named after the <em>Treponema pallidum</em> protein Tp0225. Proteins from the TpLRR class differ from the proteins in all other known LRR classes by having a flipped curvature, with the beta sheet on the convex side of the torus and irregular secondary structure instead of helices on the opposite, now concave site. TpLRR proteins also present highly divergent sequence pattern of individual repeats and can associate with specific types of additional domains. Several of the characterized proteins from this class, specifically the BspA-like proteins, were found in human bacterial and protozoan pathogens, playing an important role in the interactions between the pathogens and the host immune system. In this paper we surveyed all existing experimental structures and selected AlphaFold models of the best-known proteins containing this class of LRR repeats, analyzing the relation between the pattern of conserved residues, specific structural features and functions of these proteins.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10273536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Robust ab initio solution of the cryo-EM reconstruction problem at low resolution with small data sets 低分辨率小数据集低温电镜重建问题的鲁棒从头算方法

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.107994

Aaditya V. Rangan, Leslie Greengard

{"title":"Robust ab initio solution of the cryo-EM reconstruction problem at low resolution with small data sets","authors":"Aaditya V. Rangan, Leslie Greengard","doi":"10.1016/j.jsb.2023.107994","DOIUrl":"10.1016/j.jsb.2023.107994","url":null,"abstract":"<div><p>Single particle cryo-electron microscopy has become a critical tool in structural biology over the last decade, able to achieve atomic scale resolution in three dimensional models from hundreds of thousands of (noisy) two-dimensional projection views of particles frozen at unknown orientations. This is accomplished by using a suite of software tools to (i) identify particles in large micrographs, (ii) obtain low-resolution reconstructions, (iii) refine those low-resolution structures, and (iv) finally match the obtained electron scattering density to the constituent atoms that make up the macromolecule or macromolecular complex of interest.</p><p>Here, we focus on the second stage of the reconstruction pipeline: obtaining a low resolution model from picked particle images. Our goal is to create an algorithm that is capable of <em>ab initio</em> reconstruction from small data sets (on the order of a few thousand selected particles). More precisely, we propose an algorithm that is robust, automatic, and fast enough that it can potentially be used to assist in the assessment of particle quality as the data is being generated during the microscopy experiment.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10567851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of structural determinants of nicotinamide phosphoribosyl transferase (NAMPT) activity and substrate selectivity 烟酰胺磷酸核糖基转移酶(NAMPT)活性和底物选择性的结构决定因素鉴定

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.108004

Dorothée Houry , Arne Raasakka , Eugenio Ferrario , Marc Niere , Ersilia Bifulco , Petri Kursula , Mathias Ziegler

{"title":"Identification of structural determinants of nicotinamide phosphoribosyl transferase (NAMPT) activity and substrate selectivity","authors":"Dorothée Houry , Arne Raasakka , Eugenio Ferrario , Marc Niere , Ersilia Bifulco , Petri Kursula , Mathias Ziegler","doi":"10.1016/j.jsb.2023.108004","DOIUrl":"10.1016/j.jsb.2023.108004","url":null,"abstract":"<div><p>NAD homeostasis in mammals requires the salvage of nicotinamide (Nam), which is cleaved from NAD<sup>+</sup> by sirtuins, PARPs, and other NAD<sup>+</sup>-dependent signaling enzymes. Nam phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step in vitamin B3 salvage, whereby Nam reacts with phosphoribosyl pyrophosphate (PRPP) to form nicotinamide mononucleotide. NAMPT has a high affinity towards Nam, which is further enhanced by autophosphorylation of His247. The mechanism of this enhancement has remained unknown. Here, we present high-resolution crystal structures and biochemical data that provide reasoning for the increased affinity of the phosphorylated NAMPT for its substrate. Structural and kinetic analyses suggest a mechanism that includes Mg<sup>2+</sup> coordination by phospho-His247, such that PRPP is stabilized in a position highly favorable for catalysis. Under these conditions, nicotinic acid (NA) can serve as a substrate. Moreover, we demonstrate that a stretch of 10 amino acids, present only in NAMPTs from deuterostomes, facilitates conformational plasticity and stabilizes the chemically unstable phosphorylation of His247. Thereby the apparent substrate affinity is considerably enhanced compared to prokaryotic NAMPTs. Collectively, our study provides a structural basis for the important function of NAMPT to recycle Nam into NAD biosynthesis with high affinity.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10568128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure determination and analysis of titin A-band fibronectin type III domains provides insights for disease-linked variants and protein oligomerisation titin A-band纤维连接蛋白III型结构域的结构测定和分析为疾病相关变异和蛋白质寡聚化提供了见解

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.108009

Martin Rees , Roksana Nikoopour , Alexander Alexandrovich , Mark Pfuhl , Luis R. Lopes , Mohammed M. Akhtar , Petros Syrris , Perry Elliott , Gerry Carr-White , Mathias Gautel

{"title":"Structure determination and analysis of titin A-band fibronectin type III domains provides insights for disease-linked variants and protein oligomerisation","authors":"Martin Rees , Roksana Nikoopour , Alexander Alexandrovich , Mark Pfuhl , Luis R. Lopes , Mohammed M. Akhtar , Petros Syrris , Perry Elliott , Gerry Carr-White , Mathias Gautel","doi":"10.1016/j.jsb.2023.108009","DOIUrl":"10.1016/j.jsb.2023.108009","url":null,"abstract":"<div><p>Titin is the largest protein found in nature and spans half a sarcomere in vertebrate striated muscle. The protein has multiple functions, including in the organisation of the thick filament and acting as a molecular spring during the muscle contraction cycle. Missense variants in titin have been linked to both cardiac and skeletal myopathies. Titin is primarily composed of tandem repeats of immunoglobulin and fibronectin type III (Fn3) domains in a variety of repeat patterns; however, the vast majority of these domains have not had their high-resolution structure determined experimentally. Here, we present the crystal structures of seven wild type titin Fn3 domains and two harbouring rare missense variants reported in hypertrophic cardiomyopathy (HCM) patients. All domains present the typical Fn3 fold, with the domains harbouring variants reported in HCM patients retaining the wild-type conformation. The effect on domain folding and stability were assessed for five rare missense variants found in HCM patients: four caused thermal destabilization of between 7 and 13 °C and one prevented the folding of its domain. The structures also allowed us to locate the positions of residues whose mutations have been linked to congenital myopathies and rationalise how they convey their deleterious effects. We find no evidence of physiological homodimer formation, excluding one hypothesised mechanism as to how titin variants could exert pathological effects.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineering of brick and staple components for ordered assembly of synthetic repeat proteins 为合成重复蛋白的有序组装而设计的砖和短纤维组分

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.108012

Jessalyn Miller , Agathe Urvoas , Benoit Gigant , Malika Ouldali , Ana Arteni , Agnes Mesneau , Marie Valerio-Lepiniec , Franck Artzner , Erik Dujardin , Philippe Minard

{"title":"Engineering of brick and staple components for ordered assembly of synthetic repeat proteins","authors":"Jessalyn Miller , Agathe Urvoas , Benoit Gigant , Malika Ouldali , Ana Arteni , Agnes Mesneau , Marie Valerio-Lepiniec , Franck Artzner , Erik Dujardin , Philippe Minard","doi":"10.1016/j.jsb.2023.108012","DOIUrl":"10.1016/j.jsb.2023.108012","url":null,"abstract":"<div><p>Synthetic ɑRep repeat proteins are engineered as Brick and Staple protein pairs that together self-assemble into helical filaments. In most cases, the filaments spontaneously form supercrystals. Here, we describe an expanded series of ɑRep Bricks designed to stabilize the interaction between consecutive Bricks, to control the length of the assembled multimers, or to alter the spatial distribution of the Staple on the filaments. The effects of these Brick modifications on the assembly, on the final filament structure and on the crystal symmetry are analyzed by biochemical methods, electron microscopy and small angle X-ray scattering. We further extend the concept of Brick/Staple protein origami by designing a new type of “Janus”-like Brick protein that is equally assembled by orthogonal staples binding its inner or outer surfaces and thus ending inside or outside the filaments. The relative roles of longitudinal and lateral associations in the assembly process are discussed. This set of results demonstrates important proofs-of-principle for engineering these remarkably versatile proteins toward nanometer-to-micron scale constructions.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10221705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Binding of human Cdc123 to eIF2γ 人Cdc123与eIF2γ的结合

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.108006

Cristina Cardenal Peralta , Paul Vandroux , Lea Neumann-Arnold , Michel Panvert , Jérôme Fagart , Wolfgang Seufert , Yves Mechulam , Emmanuelle Schmitt

{"title":"Binding of human Cdc123 to eIF2γ","authors":"Cristina Cardenal Peralta , Paul Vandroux , Lea Neumann-Arnold , Michel Panvert , Jérôme Fagart , Wolfgang Seufert , Yves Mechulam , Emmanuelle Schmitt","doi":"10.1016/j.jsb.2023.108006","DOIUrl":"10.1016/j.jsb.2023.108006","url":null,"abstract":"<div><p>Eukaryotic initiation factor 2 (eIF2) plays a key role in protein synthesis and in its regulation. The assembly of this heterotrimeric factor is facilitated by Cdc123, a member of the ATP grasp family that binds the γ subunit of eIF2. Notably, some mutations related to MEHMO syndrome, an X-linked intellectual disability, affect Cdc123-mediated eIF2 assembly. The mechanism of action of Cdc123 is unclear and structural information for the human protein is awaited. Here, the crystallographic structure of human Cdc123 (Hs-Cdc123) bound to domain 3 of human eIF2γ (Hs-eIF2γD3) was determined. The structure shows that the domain 3 of eIF2γ is bound to domain 1 of Cdc123. In addition, the long C-terminal region of Hs-Cdc123 provides a link between the ATP and Hs-eIF2γD3 binding sites. A thermal shift assay shows that ATP is tightly bound to Cdc123 whereas the affinity of ADP is much smaller. Yeast cell viability experiments, western blot analysis and two-hybrid assays show that ATP is important for the function of Hs-Cdc123 in eIF2 assembly. These data and recent findings allow us to propose a refined model to explain the mechanism of action of Cdc123 in eIF2 assembly.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deep Learning-based structure modelling illuminates structure and function in uncharted regions of β-solenoid fold space 基于深度学习的结构建模揭示了β-螺线管褶皱空间中未知区域的结构和功能

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.108010

Shahram Mesdaghi , Rebecca M. Price , Jillian Madine , Daniel J. Rigden

{"title":"Deep Learning-based structure modelling illuminates structure and function in uncharted regions of β-solenoid fold space","authors":"Shahram Mesdaghi , Rebecca M. Price , Jillian Madine , Daniel J. Rigden","doi":"10.1016/j.jsb.2023.108010","DOIUrl":"10.1016/j.jsb.2023.108010","url":null,"abstract":"<div><p>Repeat proteins are common in all domains of life and exhibit a wide range of functions. One class of repeat protein contains solenoid folds where the repeating unit consists of β-strands separated by tight turns. β-solenoids have distinguishing structural features such as handedness, twist, oligomerisation state, coil shape and size which give rise to their diversity. Characterised β-solenoid repeat proteins are known to form regions in bacterial and viral virulence factors, antifreeze proteins and functional amyloids. For many of these proteins, the experimental structure has not been solved, as they are difficult to crystallise or model. Here we use various deep learning-based structure-modelling methods to discover novel predicted β-solenoids, perform structural database searches to mine further structural neighbours and relate their predicted structure to possible functions. We find both eukaryotic and prokaryotic adhesins, confirming a known functional linkage between adhesin function and the β-solenoid fold. We further identify exceptionally long, flat β-solenoid folds as possible structures of mucin tandem repeat regions and unprecedentedly small β-solenoid structures. Additionally, we characterise a novel β-solenoid coil shape, the FapC Greek key β-solenoid as well as plausible complexes between it and other proteins involved in <em>Pseudomonas</em> functional amyloid fibres.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10568161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

OpenFIBSEM: A universal API for FIBSEM control OpenFIBSEM：用于FIBSEM控制的通用API

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.107967

Patrick Cleeve , David Dierickx , Lucile Naegele , Rohit Kannachel , Lachlan Burne , Genevieve Buckley , Sergey Gorelick , James C. Whisstock , Alex de Marco

{"title":"OpenFIBSEM: A universal API for FIBSEM control","authors":"Patrick Cleeve , David Dierickx , Lucile Naegele , Rohit Kannachel , Lachlan Burne , Genevieve Buckley , Sergey Gorelick , James C. Whisstock , Alex de Marco","doi":"10.1016/j.jsb.2023.107967","DOIUrl":"10.1016/j.jsb.2023.107967","url":null,"abstract":"<div><p>This paper introduces OpenFIBSEM, a universal API to control Focused Ion Beam Scanning Electron Microscopes (FIBSEM). OpenFIBSEM aims to improve the programmability and automation of electron microscopy workflows in structural biology research. The API is designed to be cross-platform, composable, and extendable: allowing users to use any portion of OpenFIBSEM to develop or integrate with other software tools. The package provides core functionality such as imaging, movement, milling, and manipulator control, as well as system calibration, alignment, and image analysis modules. Further, a library of reusable user interface components integrated with napari is provided, ensuring easy and efficient application development.</p><p>OpenFIBSEM currently supports ThermoFisher and TESCAN hardware, with support for other manufacturers planned. To demonstrate the improved automation capabilities enabled by OpenFIBSEM, several example applications that are compatible with multiple hardware manufacturers are discussed. We argue that OpenFIBSEM provides the foundation for a cross-platform operating system and development ecosystem for FIBSEM systems. The API and applications are open-source and available on GitHub (<span>https://github.com/DeMarcoLab/fibsem</span><svg><path></path></svg>).</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10207961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenging level of rigid-body approach involving numerical elements (CHLORAINE) applied to repeated elastin peptides 具有挑战性的刚体方法涉及数值元素(氯碱)应用于重复弹性蛋白肽

IF 3 3区生物学

Journal of structural biology Pub Date : 2023-09-01 DOI: 10.1016/j.jsb.2023.107986

C. Depenveiller , H. Wong , J.M. Crowet , L. Debelle , S. Baud , M. Dauchez , N. Belloy

{"title":"Challenging level of rigid-body approach involving numerical elements (CHLORAINE) applied to repeated elastin peptides","authors":"C. Depenveiller , H. Wong , J.M. Crowet , L. Debelle , S. Baud , M. Dauchez , N. Belloy","doi":"10.1016/j.jsb.2023.107986","DOIUrl":"10.1016/j.jsb.2023.107986","url":null,"abstract":"<div><p>Elastic proteins and derived biomaterials contain numerous tandemly repeated peptides along their sequences, ranging from a few copies to hundreds. These repetitions are responsible for their biochemical, biological and biomechanical properties. These sequences are considered to be intrinsically disordered, and the variations in their behavior are actually mainly due to their high flexibility and lack of stable secondary structures originating from their unique amino acid sequences. Consequently, the simulation of elastic proteins and large elastomeric biomaterials using classical molecular dynamics is an important challenge. Here, we propose a novel approach that allows the application of the DURABIN protocol to repeated elastin-like peptides (r-ELPs) in a simple way. Four large r-ELPs were studied to evaluate our method, which was developed for simulating extracellular matrix proteins at the mesoscopic scale. After structure clustering applied on molecular dynamic trajectories of constitutive peptides (5-mers and 6-mers), the main conformations were used as starting points to define the corresponding primitives, further used as rigid body fragments in our program. Contributions derived from electrostatic and molecular hydrophobicity potentials were tested to evaluate their influence on the interactions during simple mesoscopic simulations. The CHLORAINE approach, despite the thinner granularity due to the size of the patterns used, was included in the DURABIN protocol and emerges as a promising way to simulate elastic macromolecular systems.</p></div>","PeriodicalId":17074,"journal":{"name":"Journal of structural biology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10272521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0