Proteins-Structure Function and Bioinformatics最新文献_第7页

α/β Hydrolases: Toward Unraveling Entangled Classification. α/β水解酶：解开缠结分类。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 Epub Date: 2024-12-02 DOI: 10.1002/prot.26776

Fatih Ozhelvaci, Kamil Steczkiewicz

{"title":"α/β Hydrolases: Toward Unraveling Entangled Classification.","authors":"Fatih Ozhelvaci, Kamil Steczkiewicz","doi":"10.1002/prot.26776","DOIUrl":"10.1002/prot.26776","url":null,"abstract":"α/β Hydrolase-like enzymes form a large and functionally diverse superfamily of proteins. Despite retaining a conserved structural core consisting of an eight-stranded, central β-sheet flanked with six α-helices, they display a modular architecture allowing them to perform a variety of functions, like esterases, lipases, peptidases, epoxidases, lyases, and others. At the same time, many α/β hydrolase-like families, even enzymatically distinct, share a high degree of sequence similarity. This imposes several problems for their annotation and classification, because available definitions of particular α/β hydrolase-like families overlap significantly, so the unambiguous functional assignment of these superfamily members remains a challenging task. For instance, two large and important peptidase families, namely S9 and S33, blend with lipases, epoxidases, esterases, and other enzymes unrelated to proteolysis, which hinders automatic annotations in high-throughput projects. With the use of thorough sequence and structure analyses, we newly annotate three protein families as α/β hydrolase-like and revise current classifications of the realm of α/β hydrolase-like superfamily. Based on manually curated structural superimpositions and multiple sequence and structure alignments, we comprehensively demonstrate structural conservation and diversity across the whole superfamily. Eventually, after detailed pairwise sequence similarity assessments, we develop a new clustering of the α/β hydrolases and provide a set of family profiles allowing for detailed, reliable, and automatic functional annotations of the superfamily members.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"855-870"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Myotubularin Related Proteins and the Untapped Interaction Potential of Their Disordered C-Terminal Regions. 肌小管蛋白相关蛋白及其无序c端区域未开发的相互作用潜力。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 Epub Date: 2024-11-30 DOI: 10.1002/prot.26774

Daniel Saar, Caroline L E Lennartsson, Philip Weidner, Elke Burgermeister, Birthe B Kragelund

{"title":"The Myotubularin Related Proteins and the Untapped Interaction Potential of Their Disordered C-Terminal Regions.","authors":"Daniel Saar, Caroline L E Lennartsson, Philip Weidner, Elke Burgermeister, Birthe B Kragelund","doi":"10.1002/prot.26774","DOIUrl":"10.1002/prot.26774","url":null,"abstract":"Intrinsically disordered regions (IDRs) of proteins remain understudied with enigmatic sequence features relevant to their functions. Members of the myotubularin-related protein (MTMR) family contain uncharacterized IDRs. After decades of research on their phosphatase activity, recent work on the C-terminal IDRs of MTMR7 revealed new interactions and important new functions beyond the phosphatase function. Here we take a broader look at the C-terminal domains (CTDs) of 14 human MTMRs and use bioinformatic tools and biophysical methods to ask which other functions may be probable in this protein family. The predictions show that the CTDs are disordered and carry short linear motifs (SLiMs) important for targeting of MTMRs to defined subcellular compartments and implicating them in signaling, phase separation, interaction with diverse proteins, including transcription factors and are of relevance for cancer research and neuroscience. We also present experimental methods to study the CTDs and use them to characterize the coiled coil (CC) domains of MTMR7 and MTMR9. We show homo- and hetero-oligomerization with preference for MTMR7-CC to form dimers, while MTMR9-CC forms trimers. We relate the results to sequence features and make predictions for the structural landscape of other MTMRs. Our work gives a broad insight into the so far unrecognized features and SLiMs in MTMR-CTDs, and provides the basis for more in-depth experimental research on this diverse protein family and understudied IDRs in proteins in general.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"831-854"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein-Variant-Phenotype Study of NBAS Using AlphaFold in the Aspect of SOPH Syndrome. 在SOPH综合征中应用AlphaFold研究NBAS蛋白变异表型。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 Epub Date: 2024-12-06 DOI: 10.1002/prot.26764

Leonid Zhozhikov, Filipp Vasilev, Nadezhda Maksimova

引用次数: 0

The High-Resolution Structure of a Variable Lymphocyte Receptor From Petromyzon marinus Capable of Binding to the Brain Extracellular Matrix. 能与脑细胞外基质结合的海百合可变淋巴细胞受体的高分辨率结构。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 Epub Date: 2024-11-27 DOI: 10.1002/prot.26768

Elizabeth A Appelt, James B Thoden, Seth A Gehrke, Hannah D Bachmeier, Ivan Rayment, Eric V Shusta, Hazel M Holden

{"title":"The High-Resolution Structure of a Variable Lymphocyte Receptor From Petromyzon marinus Capable of Binding to the Brain Extracellular Matrix.","authors":"Elizabeth A Appelt, James B Thoden, Seth A Gehrke, Hannah D Bachmeier, Ivan Rayment, Eric V Shusta, Hazel M Holden","doi":"10.1002/prot.26768","DOIUrl":"10.1002/prot.26768","url":null,"abstract":"Variable lymphocyte receptors (VLRs) are antigen receptors derived from the adaptive immune system of jawless vertebrates such as lamprey ( Petromyzon marinus ). First discovered in 2004, VLRs have been the subject of numerous biochemical and structural investigations. Due to their unique antigen binding properties, VLRs have been leveraged as possible drug delivery agents. One such VLR, previously identified and referred to as P1C10, was shown to bind to the brain extracellular matrix. Here, we present the high-resolution X-ray crystal structure of this VLR determined to 1.3 Å resolution. The fold is dominated by a six-stranded mixed β-sheet which provides a concave surface for possible antigen binding. Electron density corresponding to a 4-(2-hydroxyethyl)piperazine-1-propanesulfonic acid buffer molecule (HEPPS) was found in this region. By comparing the P1C10 molecular architecture and its buffer binding residues with those of other VLRs previously reported, it was possible to illustrate how this unique class of proteins can accommodate diverse binding partners. Additionally, we provide an analysis of the experimentally determined structure compared to the models generated by the commonly used AlphaFold and iTASSER structure prediction software packages.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"801-811"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Using Short Molecular Dynamics Simulations to Determine the Important Features of Interactions in Antibody-Protein Complexes. 利用短分子动力学模拟确定抗体-蛋白质复合物相互作用的重要特征。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 Epub Date: 2024-11-27 DOI: 10.1002/prot.26773

A Clay Richard, Robert J Pantazes

{"title":"Using Short Molecular Dynamics Simulations to Determine the Important Features of Interactions in Antibody-Protein Complexes.","authors":"A Clay Richard, Robert J Pantazes","doi":"10.1002/prot.26773","DOIUrl":"10.1002/prot.26773","url":null,"abstract":"The last few years have seen the rapid proliferation of machine learning methods to design binding proteins. Although these methods have shown large increases in experimental success rates compared to prior approaches, the majority of their predictions fail when they are experimentally tested. It is evident that computational methods still struggle to distinguish the features of real protein binding interfaces from false predictions. Short molecular dynamics simulations of 20 antibody-protein complexes were conducted to identify features of interactions that should occur in binding interfaces. Intermolecular salt bridges, hydrogen bonds, and hydrophobic interactions were evaluated for their persistences, energies, and stabilities during the simulations. It was found that only the hydrogen bonds where both residues are stabilized in the bound complex are expected to persist and meaningfully contribute to binding between the proteins. In contrast, stabilization was not a requirement for salt bridges and hydrophobic interactions to persist. Still, interactions where both residues are stabilized in the bound complex persist significantly longer and have significantly stronger energies than other interactions. Two hundred and twenty real antibody-protein complexes and 8194 decoy complexes were used to train and test a random forest classifier using the features of expected persistent interactions identified in this study and the macromolecular features of interaction energy (IE), buried surface area (BSA), IE/BSA, and shape complementarity. It was compared to a classifier trained only on the expected persistent interaction features and another trained only on the macromolecular features. Inclusion of the expected persistent interaction features reduced the false positive rate of the classifier by two- to five-fold across a range of true positive classification rates.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"812-830"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142735041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural Basis for the Essential Role of Ca²⁺ in the Lytic Activity of Staphylococcus aureus PlyGRCS Endolysin Targeting Methicillin-Resistant Staphylococcus aureus. Ca2+在靶向耐甲氧西林金黄色葡萄球菌的金黄色葡萄球菌PlyGRCS内溶素裂解活性中重要作用的结构基础

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 Epub Date: 2024-12-11 DOI: 10.1002/prot.26777

Gopinatha Krishnappa, Harshitha Nagaraj, Harshavardini Bakthavatsalam SureshKumar, Mitali Mandal, Sivaraman Padavattan, Veenakumari Haradara Bahubali, Saravanamuthu Thiyagarajan, Balasundaram Padmanabhan

{"title":"Structural Basis for the Essential Role of Ca2+ in the Lytic Activity of Staphylococcus aureus PlyGRCS Endolysin Targeting Methicillin-Resistant Staphylococcus aureus.","authors":"Gopinatha Krishnappa, Harshitha Nagaraj, Harshavardini Bakthavatsalam SureshKumar, Mitali Mandal, Sivaraman Padavattan, Veenakumari Haradara Bahubali, Saravanamuthu Thiyagarajan, Balasundaram Padmanabhan","doi":"10.1002/prot.26777","DOIUrl":"10.1002/prot.26777","url":null,"abstract":"Staphylococcus aureus causes a wide range of infections, from mild skin conditions to severe, life-threatening diseases. Bacteriophage endolysins exhibit a selective capacity to degrade the peptidoglycan layer of Gram-positive bacteria, making promising biotherapeutic agents against antibiotic-resistant infections. PlyGRCS, a specific endolysin derived from S. aureus, comprises a catalytic CHAP domain and a cell-wall binding SH3_5 domain connected by a linker. Ca2+ ions are essential for the CHAP domain's catalytic function. The crystal structure of PlyGRCS, determined in the absence of Ca2+ and refined to a resolution of 1.67 Å, revealed significant conformational changes in the Ca2+ binding site. Antimicrobial assays with Ca2+-deficient PlyGRCS and mutants targeting key residues in the catalytic and Ca2+ binding regions highlighted the importance of specific functional residues for lytic activity against methicillin-resistant Staphylococcus aureus (MRSA). These structural and microbial studies provide valuable insights into the critical residues contributing to PlyGRCS's bacteriolytic efficacy against MRSA.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"920-933"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142807171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Protein Complex Structure Prediction With AlphaFold-Enhanced HDOCK in CAPRI Rounds 47-55. 利用alphafold增强的HDOCK预测CAPRI蛋白复合体结构47-55。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 DOI: 10.1002/prot.26823

Hao Li, Peicong Lin, Yurui Li, Sheng-You Huang

引用次数: 0

Correction to "AbDPP: Target-Oriented Antibody Design With Pretraining and Prior Biological Structure Knowledge". 修正“AbDPP：基于预训练和先验生物结构知识的靶向抗体设计”。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 Epub Date: 2024-12-02 DOI: 10.1002/prot.26775

引用次数: 0

MuGger Toxins: Exploring the Selective Binding Mechanism of Clostridial Glucosyltransferase Toxin B and Host GTPases. MuGger毒素：探索梭菌糖基转移酶毒素B与宿主gtp酶的选择性结合机制。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 Epub Date: 2024-12-13 DOI: 10.1002/prot.26770

Damla Nur Camli, Haci Aslan Onur Iscil, Saliha Ece Acuner

{"title":"MuGger Toxins: Exploring the Selective Binding Mechanism of Clostridial Glucosyltransferase Toxin B and Host GTPases.","authors":"Damla Nur Camli, Haci Aslan Onur Iscil, Saliha Ece Acuner","doi":"10.1002/prot.26770","DOIUrl":"10.1002/prot.26770","url":null,"abstract":"(a) Clostridioides difficile ( C. difficile ) bacterium can cause severe diarrhea and its over-colonization in the host's intestinal tract lead to the development of pseudomembranous colitis, generally due to antibiotic usage. The primary exotoxins involved are toxin A (TcdA) and toxin B (TcdB), the latter being more pathogenic. TcdB has glucosyltransferase activity and mediates monoglycosylation by targeting host cell enzymes (mainly Rho and Ras family of GTPases) with differential selectivity. Here, we aim to provide structural and dynamic insights into how TcdB impacts the host's intestinal epithelial cells focusing on the glycosylation mechanism of Rho GTPases, Cdc42, and Rac1, at the molecular level. To this aim, we modeled the unknown TcdB-host protein complex structures, based on the available experimental structures of TcdB, through protein-protein docking. Then, we elaborated on TcdB-Rho GTPase models as TcdB is known to selectively interact with GDP-bound inactive states of Rho GTPases, over the GTP-bound active ones, but the mechanism is unclear. Through a total of 6 μs-long molecular dynamics simulation of TcdB and GTP/GDP-bound Rac1 and Cdc42 complexes, TcdB's selective binding mechanism was revealed for Rac1. TcdB-Rac1 complexes were further analyzed with enhanced sampling techniques such as well-tempered metadynamics simulations and umbrella sampling to reveal selective binding mechanism between TcdB and GDP-bound Rac1. Our results show that TcdB selectively binds to GDP-bound Rac1, over the GTP-bound one, driven by its affinity for the Mg2+ ion. A destabilized Mg2+ ion incapable of coordinating GDP disrupts Rac1's GTPase function, shedding light on the molecular basis of TcdB's pathogenic effects.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"934-944"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Conserved and Unique Mitochondrial Target Sequence of TRPV4 Can Independently Regulate Mitochondrial Functions. 保守而独特的TRPV4线粒体靶序列可独立调控线粒体功能。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2025-04-01 Epub Date: 2024-12-08 DOI: 10.1002/prot.26772

Tusar Kanta Acharya, Parnasree Mahapatra, Shamit Kumar, Nishant Kumar Dubey, Srujanika Rajalaxmi, Arijit Ghosh, Ashutosh Kumar, Chandan Goswami

{"title":"Conserved and Unique Mitochondrial Target Sequence of TRPV4 Can Independently Regulate Mitochondrial Functions.","authors":"Tusar Kanta Acharya, Parnasree Mahapatra, Shamit Kumar, Nishant Kumar Dubey, Srujanika Rajalaxmi, Arijit Ghosh, Ashutosh Kumar, Chandan Goswami","doi":"10.1002/prot.26772","DOIUrl":"10.1002/prot.26772","url":null,"abstract":"Though mitochondria have their own genome and protein synthesis machineries, the majority of the mitochondrial proteins are actually encoded by the nuclear genome. Most of these mitochondrial proteins are imported into specific compartments of the mitochondria due to their mitochondrial target sequence (MTS). Unlike the nuclear target sequence, the MTS of most of the mitochondrial localized proteins remain poorly understood, mainly due to their variability, heterogeneity, unconventional modes of action, mitochondrial potential-dependent transport, and other complexities. Recently, we reported that transient receptor potential vanilloid subtype 4 (TRPV4), a thermosensitive cation channel, is physically located at the mitochondria. Here we characterize a small segment (AA 592-630) located at the TM4-loop4-TM5 segment of TRPV4 that acts as a novel MTS. The same region remains highly conserved in all vertebrates and contains a large number of point mutations each of which causes an diverse spectrum of diseases in human. Using confocal and super-resolution microscopy, we show that this MTS of TRPV4 or its mutants localizes to the mitochondria independently and also induces functional and quantitative changes in the mitochondria. By using conformal microscopy, we could detect the presence of the MTS region within the isolated mitochondria. These findings may be important to understand the complexity of MTS and TRPV4-induced channelopathies better.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":"908-919"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0