Current Research in Structural Biology最新文献_第2页

GraSp-PSN: A web server for graph spectra based analysis of protein structure networks GraSp-PSN：基于图谱分析蛋白质结构网络的网络服务器

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100147

Vasundhara Gadiyaram, Vasam Manjveekar Prabantu, Arinnia Anto Manjaly , Ananth Muthiah, Saraswathi Vishveshwara

{"title":"GraSp-PSN: A web server for graph spectra based analysis of protein structure networks","authors":"Vasundhara Gadiyaram, Vasam Manjveekar Prabantu, Arinnia Anto Manjaly , Ananth Muthiah, Saraswathi Vishveshwara","doi":"10.1016/j.crstbi.2024.100147","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100147","url":null,"abstract":"<div><p>The function of a protein is most of the time achieved due to minute conformational changes in its structure due to ligand binding or environmental changes or other interactions. Hence the analysis of structure of proteins should go beyond the analysis of mere atom contacts and should include the emergent global structure as a whole. This can be achieved by graph spectra based analysis of protein structure networks. GraSp-PSN is a web server that can assist in (1) acquiring weighted protein structure network (PSN) and network parameters ranging from atomic level to global connectivity from the three dimensional coordinates of a protein, (2) generating scores for comparison of a pair of protein structures with detailed information of local to global connectivity, and (3) assigning perturbation scores to the residues and their interactions, that can prioritise them in terms of residue clusters. The methods implemented in the server are generic in nature and can be used for comparing networks in any discipline by uploading adjacency matrices in the server. The webserver can be accessed using the following link: <span>https://pople.mbu.iisc.ac.in/</span><svg><path></path></svg>.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000242/pdfft?md5=739c6cab73a5919caa6cedc6fe5317c7&pid=1-s2.0-S2665928X24000242-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140879520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of drug resistance in HIV-1 protease subtype C in the presence of Atazanavir 阿扎那韦作用下 HIV-1 蛋白酶亚型 C 的耐药机制

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100132

S.V. Sankaran , Sowmya R. Krishnan , Yasien Sayed , M. Michael Gromiha

{"title":"Mechanism of drug resistance in HIV-1 protease subtype C in the presence of Atazanavir","authors":"S.V. Sankaran , Sowmya R. Krishnan , Yasien Sayed , M. Michael Gromiha","doi":"10.1016/j.crstbi.2024.100132","DOIUrl":"10.1016/j.crstbi.2024.100132","url":null,"abstract":"<div><p>AIDS is one of the deadliest diseases in the history of humankind caused by HIV. Despite the technological development, curtailing the viral infection inside human host still remains a challenge. Therapies such as HAART uses a combination of drugs to inhibit the viral activity. One of the important targets includes HIV protease and inhibiting its activity will minimize the production of mature structural proteins. However, the genetic diversity and the occurrence of drug resistant mutations adds complexity to effective drug design. In this study, we aimed at understanding the drug binding mechanism of one such subtype, namely subtype C and its insertion variant L38HL. We performed multiple molecular dynamics simulations along with binding free energy analysis of wild-type and L38HL bound to Atazanavir (ATV). From the analysis, we revealed that the insertion alters the hydrogen bond and hydrophobic interaction networks. The alterations in the interaction networks increase flexibility at the hinge-fulcrum interface. Further, the effects of these changes affect flap tip curling. Moreover, the changes in the hinge-fulcrum-cantilever interface alters the concerted motion of the functional regions leading to change in the direction of flap movement thus causing a subtle change in the active site volume. Additionally, formation of intramolecular hydrogen bonds in the ATV docked to L38HL restricted the movement of R1 and R2 groups thereby altering the interactions. Overall, the changes in the flexibility of flap together with the changes in the active site volume and compactness of the ligand provide insights for increased binding affinity of ATV with L38HL.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000096/pdfft?md5=306b72342c5038d99b11a59449839fde&pid=1-s2.0-S2665928X24000096-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139966445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure-function analyses reveal Arabidopsis thaliana HDA7 to be an inactive histone deacetylase 结构-功能分析揭示拟南芥 HDA7 是一种非活性组蛋白去乙酰化酶

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100136

Ketul Saharan , Somanath Baral , Nausad Hossain Shaikh , Dileep Vasudevan

{"title":"Structure-function analyses reveal Arabidopsis thaliana HDA7 to be an inactive histone deacetylase","authors":"Ketul Saharan , Somanath Baral , Nausad Hossain Shaikh , Dileep Vasudevan","doi":"10.1016/j.crstbi.2024.100136","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100136","url":null,"abstract":"<div><p>Histone deacetylases (HDACs), responsible for the removal of acetyl groups from histone tails, are important epigenetic factors. They play a critical role in the regulation of gene expression and are significant in the context of plant growth and development. The Rpd3/Hda1 family of HDACs is reported to regulate key biological processes in plants, such as stress response, seed, embryonic, and floral development. Here, we characterized <em>Arabidopsis thaliana</em> HDA7, a Class I, Rpd3/Hda1 family HDAC. SAXS and AUC results show that the recombinantly expressed and purified histone deacetylase domain of AtHDA7 exists as a monomer in solution. Further, the crystal structure showed AtHDA7 to fold into the typical α/β arginase fold, characteristic of Rpd3/Hda1 family HDACs. Sequence analysis revealed that the Asp and His residues of the catalytic ‘XDXH’ motif present in functional Rpd3/Hda1 family HDACs are mutated to Gly and Pro, respectively, in AtHDA7, suggesting that it might be catalytically inactive. The Asp and His residues are important for Zn<sup>2+</sup>-binding. Not surprisingly, the crystal structure did not have Zn<sup>2+</sup> bound in the catalytic pocket, which is essential for the HDAC activity. Further, our <em>in vitro</em> activity assay revealed AtHDA7 to be inactive as an HDAC. A search in the sequence databases suggested that homologs of AtHDA7 are found exclusively in the Brassicaceae family to which Arabidopsis belongs. It is possible that HDA7 descended from HDA6 through whole genome duplication and triplication events during evolution, as suggested in a previous phylogenetic study.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000138/pdfft?md5=9613b556bf68eed37357f5c1262013ad&pid=1-s2.0-S2665928X24000138-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140014121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Experimental methods to study the structure and dynamics of intrinsically disordered regions in proteins 研究蛋白质内在无序区结构和动力学的实验方法

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100138

Snigdha Maiti , Aakanksha Singh, Tanisha Maji, Nikita V. Saibo, Soumya De

{"title":"Experimental methods to study the structure and dynamics of intrinsically disordered regions in proteins","authors":"Snigdha Maiti , Aakanksha Singh, Tanisha Maji, Nikita V. Saibo, Soumya De","doi":"10.1016/j.crstbi.2024.100138","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100138","url":null,"abstract":"<div><p>Eukaryotic proteins often feature long stretches of amino acids that lack a well-defined three-dimensional structure and are referred to as intrinsically disordered proteins (IDPs) or regions (IDRs). Although these proteins challenge conventional structure-function paradigms, they play vital roles in cellular processes. Recent progress in experimental techniques, such as NMR spectroscopy, single molecule FRET, high speed AFM and SAXS, have provided valuable insights into the biophysical basis of IDP function. This review discusses the advancements made in these techniques particularly for the study of disordered regions in proteins. In NMR spectroscopy new strategies such as <sup>13</sup>C detection, non-uniform sampling, segmental isotope labeling, and rapid data acquisition methods address the challenges posed by spectral overcrowding and low stability of IDPs. The importance of various NMR parameters, including chemical shifts, hydrogen exchange rates, and relaxation measurements, to reveal transient secondary structures within IDRs and IDPs are presented. Given the high flexibility of IDPs, the review outlines NMR methods for assessing their dynamics at both fast (ps-ns) and slow (μs-ms) timescales. IDPs exert their functions through interactions with other molecules such as proteins, DNA, or RNA. NMR-based titration experiments yield insights into the thermodynamics and kinetics of these interactions. Detailed study of IDPs requires multiple experimental techniques, and thus, several methods are described for studying disordered proteins, highlighting their respective advantages and limitations. The potential for integrating these complementary techniques, each offering unique perspectives, is explored to achieve a comprehensive understanding of IDPs.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000151/pdfft?md5=f40c41eba2b2db9f84e2f421c05b2b24&pid=1-s2.0-S2665928X24000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140807179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Alternate conformations found in protein structures implies biological functions: A case study using cyclophilin A 蛋白质结构中发现的替代构象意味着生物功能：利用环纤蛋白 A 进行案例研究

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100145

Chandrasekaran Palaniappan , Santhosh Rajendran , Kanagaraj Sekar

{"title":"Alternate conformations found in protein structures implies biological functions: A case study using cyclophilin A","authors":"Chandrasekaran Palaniappan , Santhosh Rajendran , Kanagaraj Sekar","doi":"10.1016/j.crstbi.2024.100145","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100145","url":null,"abstract":"<div><p>Protein dynamics linked to numerous biomolecular functions, such as ligand binding, allosteric regulation, and catalysis, must be better understood at the atomic level. Reactive atoms of key residues drive a repertoire of biomolecular functions by flipping between alternate conformations or conformational substates, seldom found in protein structures. Probing such sparsely sampled alternate conformations would provide mechanistic insight into many biological functions. We are therefore interested in evaluating the instance of amino acids adopted alternate conformations, either in backbone or side-chain atoms or in both. Accordingly, over 70000 protein structures appear to contain alternate conformations only 'A' and 'B' for any atom, particularly the instance of amino acids that adopted alternate conformations are more for Arg, Cys, Met, and Ser than others. The resulting protein structure analysis depicts that amino acids with alternate conformations are mainly found in the helical and β-regions and are often seen in high-resolution X-ray crystal structures. Furthermore, a case study on human cyclophilin A (CypA) was performed to explain the pre-existing intrinsic dynamics of catalytically critical residues from the CypA and how such intrinsic dynamics perturbed upon Ser99Thr mutation using molecular dynamics simulations on the ns-μs timescale. Simulation results demonstrated that the Ser99Thr mutation had impaired the alternate conformations or the catalytically productive micro-environment of Phe113, mimicking the experimentally observed perturbation captured by X-ray crystallography. In brief, a deeper comprehension of alternate conformations adopted by the amino acids may shed light on the interplay between protein structure, dynamics, and function.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000229/pdfft?md5=99f78944ded3d8b7139bf3f324f58946&pid=1-s2.0-S2665928X24000229-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140638479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structure and function of the light-protective orange carotenoid protein families 橙色类胡萝卜素光保护蛋白家族的结构和功能

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100141

Teresa M. García-Oneto , Claudia Moyano-Bellido , M. Agustina Domínguez-Martín

{"title":"Structure and function of the light-protective orange carotenoid protein families","authors":"Teresa M. García-Oneto , Claudia Moyano-Bellido , M. Agustina Domínguez-Martín","doi":"10.1016/j.crstbi.2024.100141","DOIUrl":"10.1016/j.crstbi.2024.100141","url":null,"abstract":"<div><p>Orange carotenoid proteins (OCPs) are unique photoreceptors that are critical for cyanobacterial photoprotection. Upon exposure to blue-green light, OCPs are activated from a stable orange form, OCP<sup>O</sup>, to an active red form, OCP<sup>R</sup>, which binds to phycobilisomes (PBSs) and performs photoprotective non-photochemical quenching (NPQ). OCPs can be divided into three main families: the most abundant and best studied OCP1, and two others, OCP2 and OCP3, which have different activation and quenching properties and are yet underexplored. Crystal structures have been acquired for the three OCP clades, providing a glimpse into the conformational underpinnings of their light-absorption and energy dissipation attributes. Recently, the structure of the PBS-OCP<sup>R</sup> complex has been obtained allowing for an unprecedented insight into the photoprotective action of OCPs. Here, we review the latest findings in the field that have substantially improved our understanding of how cyanobacteria protect themselves from the toxic consequences of excess light absorption. Furthermore, current research is applying the structure of OCPs to bio-inspired optogenetic tools, to function as carotenoid delivery devices, as well as engineering the NPQ mechanism of cyanobacteria to enhance their photosynthetic biomass production.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000187/pdfft?md5=94fcdc3bbbf23bc37abf0f283dfea5e5&pid=1-s2.0-S2665928X24000187-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Membrane binding and lipid-protein interaction of the C2 domain from coagulation factor V 凝血因子 V C2 结构域的膜结合和脂质-蛋白质相互作用

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100149

Y. Zenmei Ohkubo , Peter W. Radulovic , Albert N. Kahira , Jesper J. Madsen

{"title":"Membrane binding and lipid-protein interaction of the C2 domain from coagulation factor V","authors":"Y. Zenmei Ohkubo , Peter W. Radulovic , Albert N. Kahira , Jesper J. Madsen","doi":"10.1016/j.crstbi.2024.100149","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100149","url":null,"abstract":"<div><p>Anchoring of coagulation factors to anionic regions of the membrane involves the C2 domain as a key player. The rate of enzymatic reactions of the coagulation factors is increased by several orders of magnitude upon membrane binding. However, the precise mechanisms behind the rate acceleration remain unclear, primarily because of a lack of understanding of the conformational dynamics of the C2-containing factors and corresponding complexes. We elucidate the membrane-bound form of the C2 domain from human coagulation factor V (FV–C2) by characterizing its membrane binding the specific lipid-protein interactions. Employing all-atom molecular dynamics simulations and leveraging the highly mobile membrane-mimetic (HMMM) model, we observed spontaneous binding of FV-C2 to a phosphatidylserine (PS)-containing membrane within 2–25 ns across twelve independent simulations. FV-C2 interacted with the membrane through three loops (spikes 1–3), achieving a converged, stable orientation. Multiple HMMM trajectories of the spontaneous membrane binding provided extensive sampling and ample data to examine the membrane-induced effects on the conformational dynamics of C2 as well as specific lipid-protein interactions. Despite existing crystal structures representing presumed “open” and “closed” states of FV-C2, our results revealed a continuous distribution of structures between these states, with the most populated structures differing from both “open” and “closed” states observed in crystal environments. Lastly, we characterized a putative PS-specific binding site formed by K23, Q48, and S78 located in the groove enclosed by spikes 1–3 (PS-specificity pocket), suggesting a different orientation of a bound headgroup moiety compared to previous proposals based upon analysis of static crystal structures.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000266/pdfft?md5=e8ab6e6a13338f75043488820ca37b17&pid=1-s2.0-S2665928X24000266-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140879519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

ANN based prediction of ligand binding sites outside deep cavities to facilitate drug designing 基于 ANN 的深腔外配体结合位点预测，促进药物设计

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100144

Kalpana Singh, Yashpal Singh Malik

{"title":"ANN based prediction of ligand binding sites outside deep cavities to facilitate drug designing","authors":"Kalpana Singh, Yashpal Singh Malik","doi":"10.1016/j.crstbi.2024.100144","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100144","url":null,"abstract":"<div><p>The ever-changing environmental conditions and pollution are the prime reasons for the onset of several emerging and re-merging diseases. This demands the faster designing of new drugs to curb the deadly diseases in less waiting time to cure the animals and humans. Drug molecules interact with only protein surface on specific locations termed as ligand binding sites (LBS). Therefore, the knowledge of LBS is required for rational drug designing. Existing geometrical LBS prediction methods rely on search of cavities based on the fact that 83% of the LBS found in deep cavities, however, these methods usually fail where LBS localize outside deep cavities. To overcome this challenge, the present work provides an artificial neural network (ANN) based method to predict LBS outside deep cavities in animal proteins including human to facilitate drug designing. In the present work a feed-forward backpropagation neural network was trained by utilizing 38 structural, atomic, physiochemical, and evolutionary discriminant features of LBS and non-LBS residues localized in the extracted roughest patch on protein surface. The performance of this ANN based prediction method was found 76% better for those proteins where cavity subspace (extracted by MetaPocket 2.0, a consensus method) failed to predict LBS due to their localization outside the deep cavities. The prediction of LBS outside deep cavities will facilitate in drug designing for the proteins where it is not possible due to lack of LBS information as the geometrical LBS prediction methods rely on extraction of deep cavities.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000217/pdfft?md5=6488d8469a0b3dff9732a9f2ecb71a87&pid=1-s2.0-S2665928X24000217-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140606935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 and functional insights of sortases and their interactions with antivirulence compounds 分选酶的结构和功能及其与抗病毒化合物相互作用的深入研究

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100152

Sowmiya Sri Sivaramalingam , Deepsikha Jothivel , Deenadayalan Karaiyagowder Govindarajan , Lohita Kadirvelu , Muthusaravanan Sivaramakrishnan , Dhivia Dharshika Chithiraiselvan , Kumaravel Kandaswamy

{"title":"Structural and functional insights of sortases and their interactions with antivirulence compounds","authors":"Sowmiya Sri Sivaramalingam , Deepsikha Jothivel , Deenadayalan Karaiyagowder Govindarajan , Lohita Kadirvelu , Muthusaravanan Sivaramakrishnan , Dhivia Dharshika Chithiraiselvan , Kumaravel Kandaswamy","doi":"10.1016/j.crstbi.2024.100152","DOIUrl":"10.1016/j.crstbi.2024.100152","url":null,"abstract":"<div><p>Sortase proteins play a crucial role as integral membrane proteins in anchoring bacterial surface proteins by recognizing them through a Cell-Wall Sorting (CWS) motif and cleaving them at specific sites before initiating pilus assembly. Both sortases and their substrate proteins are major virulence factors in numerous Gram-positive pathogens, making them attractive targets for antimicrobial intervention. Recognizing the significance of virulence proteins, a comprehensive exploration of their structural and functional characteristics is essential to enhance our understanding of pilus assembly in diverse Gram-positive bacteria. Therefore, this review article discusses the structural features of different classes of sortases and pilin proteins, primarily serving as substrates for sortase-assembled pili. Moreover, it thoroughly examines the molecular-level interactions between sortases and their inhibitors, providing insights from both structural and functional perspectives. In essence, this review article will provide a contemporary and complete understanding of both sortase pathways and various strategies to target them effectively to counteract the virulence.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000291/pdfft?md5=db64ca05515c00e67922cda0b3897a38&pid=1-s2.0-S2665928X24000291-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141395433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 impact of SARS-CoV-2 spike mutation on peptide presentation is HLA allomorph-specific SARS-CoV-2尖峰突变对肽呈现的影响具有 HLA 同形异体特异性

IF 2.8

Current Research in Structural Biology Pub Date : 2024-01-01 DOI: 10.1016/j.crstbi.2024.100148

You Min Ahn , Janesha C. Maddumage , Emma J. Grant , Demetra S.M. Chatzileontiadou , W.W.J. Gihan Perera , Brian M. Baker , Christopher Szeto , Stephanie Gras

{"title":"The impact of SARS-CoV-2 spike mutation on peptide presentation is HLA allomorph-specific","authors":"You Min Ahn , Janesha C. Maddumage , Emma J. Grant , Demetra S.M. Chatzileontiadou , W.W.J. Gihan Perera , Brian M. Baker , Christopher Szeto , Stephanie Gras","doi":"10.1016/j.crstbi.2024.100148","DOIUrl":"https://doi.org/10.1016/j.crstbi.2024.100148","url":null,"abstract":"<div><p>CD8<sup>+</sup> T cells are crucial for viral elimination and recovery from viral infection. Nonetheless, the current understanding of the T cell response to SARS-CoV-2 at the antigen level remains limited. The Spike protein is an external structural protein that is prone to mutations, threatening the efficacy of current vaccines. Therefore, we have characterised the immune response towards the immunogenic Spike-derived peptide (S<sub>976-984</sub>, VLNDILSRL), restricted to the HLA-A*02:01 molecule, which is mutated in both Alpha (S982A) and Omicron BA.1 (L981F) variants of concern. We determined that the mutation in the Alpha variant (S982A) impacted both the stability and conformation of the peptide, bound to HLA-A*02:01, in comparison to the original S<sub>976-984</sub>. We identified a longer and overlapping immunogenic peptide (S<sub>975-984</sub>, SVLNDILSRL) that could be presented by HLA-A*02:01, HLA-A*11:01 and HLA-B*13:01 allomorphs. We showed that S975-specific CD8<sup>+</sup> T cells were weakly cross-reactive to the mutant peptides despite their similar conformations when presented by HLA-A*11:01. Altogether, our results show that the impact of SARS-CoV-2 mutations on peptide presentation is HLA allomorph-specific, and that post vaccination there are T cells able to react and cross-react towards the variant of concern peptides.</p></div>","PeriodicalId":10870,"journal":{"name":"Current Research in Structural Biology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2665928X24000254/pdfft?md5=68e3219bc99c70680b9c5efa9ff8b0ce&pid=1-s2.0-S2665928X24000254-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140824840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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