Journal of Structural Biology: X最新文献_第2页

SidF, a dual substrate N5-acetyl-N5-hydroxy-L-ornithine transacetylase involved in Aspergillus fumigatus siderophore biosynthesis 参与烟曲霉嗜铁菌生物合成的双底物n5 -乙酰- n5 -羟基- l-鸟氨酸转乙酰化酶。

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-12-26 DOI: 10.1016/j.yjsbx.2024.100119

Thanalai Poonsiri , Jan Stransky , Nicola Demitri , Hubertus Haas , Michele Cianci , Stefano Benini

{"title":"SidF, a dual substrate N5-acetyl-N5-hydroxy-L-ornithine transacetylase involved in Aspergillus fumigatus siderophore biosynthesis","authors":"Thanalai Poonsiri , Jan Stransky , Nicola Demitri , Hubertus Haas , Michele Cianci , Stefano Benini","doi":"10.1016/j.yjsbx.2024.100119","DOIUrl":"10.1016/j.yjsbx.2024.100119","url":null,"abstract":"<div><div>Siderophore-mediated iron acquisition is essential for the virulence of <em>Aspergillus fumigatus</em>, a fungus causing life-threatening aspergillosis. Drugs targeting the siderophore biosynthetic pathway could help improve disease management. The transacetylases SidF and SidL generate intermediates for different siderophores in <em>A. fumigatus</em>. <em>A. fumigatus</em> has a yet unidentified transacetylase that complements SidL during iron deficiency in SidL-lacking mutants.</div><div>We present the first X-ray structure of SidF, revealing a two-domain architecture with tetrameric assembly. The N-terminal domain contributes to protein solubility and oligomerization, while the C-terminal domain containing the GCN5-related N-acetyltransferase (GNAT) motif is crucial for the enzymatic activity and mediates oligomer formation. Notably, AlphaFold modelling demonstrates structural similarity between SidF and SidL. Enzymatic assays showed that SidF can utilize acetyl-CoA as a donor, previously thought to be a substrate of SidL but not SidF, and selectively uses N5-hydroxy-L-ornithine as an acceptor.</div><div>This study elucidates the structure of SidF and reveals its role in siderophore biosynthesis. We propose SidF as the unknown transacetylase complementing SidL activity, highlighting its central role in <em>A. fumigatus</em> siderophore biosynthesis. Investigation of this uncharacterized GNAT protein enhances our understanding of fungal virulence and holds promise for its potential application in developing antifungal therapies.</div></div>","PeriodicalId":17238,"journal":{"name":"Journal of Structural Biology: X","volume":"11 ","pages":"Article 100119"},"PeriodicalIF":3.5,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023943","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

Highly versatile small virus-encoded proteins in cellular membranes: A structural perspective on how proteins’ inherent conformational plasticity couples with host membranes’ properties to control cellular processes 细胞膜中高度通用的小病毒编码蛋白：蛋白质固有构象可塑性如何与宿主膜特性偶联以控制细胞过程的结构视角

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-12-11 DOI: 10.1016/j.yjsbx.2024.100117

Arvin Saffarian Delkhosh , Elaheh Hadadianpour , Md Majharul Islam, Elka R. Georgieva

{"title":"Highly versatile small virus-encoded proteins in cellular membranes: A structural perspective on how proteins’ inherent conformational plasticity couples with host membranes’ properties to control cellular processes","authors":"Arvin Saffarian Delkhosh , Elaheh Hadadianpour , Md Majharul Islam, Elka R. Georgieva","doi":"10.1016/j.yjsbx.2024.100117","DOIUrl":"10.1016/j.yjsbx.2024.100117","url":null,"abstract":"<div><div>We investigated several small viral proteins that reside and function in cellular membranes. These proteins belong to the viroporin family because they assemble into ion-conducting oligomers. However, despite forming similar oligomeric structures with analogous functions, these proteins have diverse amino acid sequences. In particular, the amino acid compositions of the proposed channel-forming transmembrane (TM) helices are vastly different—some contain residues (e.g., His, Trp, Asp, Ser) that could facilitate cation transport. Still, other viroporins’ TM helices encompass exclusively hydrophobic residues; therefore, it is difficult to explain their channels’ activity, unless other mechanisms (e.g., involving a negative lipid headgroups and/or membrane destabilization) take place. For this study, we selected the M2, Vpu, E, p13II, p7, and 2B proteins from the influenza A, HIV-1, human T-cell leukemia, hepatitis C, and picorna viruses, respectively. We provide a brief overview of the current knowledge about these proteins’ structures as well as remaining questions about more comprehensive understanding of their structures, conformational dynamics, and function. Finally, we outline strategies to utilize a multi-prong structural and computational approach to overcome current deficiencies in the knowledge about these proteins.</div></div>","PeriodicalId":17238,"journal":{"name":"Journal of Structural Biology: X","volume":"11 ","pages":"Article 100117"},"PeriodicalIF":3.5,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11714672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971424","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

Corrigendum to “Minimizing ice contamination during specimen preparation for cryo-soft X-ray tomography and cryo-electron tomography” [J. Struct. Biol.: X 10(2024) 100113] 对 "尽量减少低温软 X 射线断层成像和低温电子断层成像标本制备过程中的冰污染 "的更正[J. Struct.

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-10-30 DOI: 10.1016/j.yjsbx.2024.100115

Chia-Chun Hsieh, Zi-Jing Lin, Lee-Jene Lai

引用次数: 0

Editorial by Natalie Reznikov [for Buss et al., “Hierarchical organization of bone in three dimensions: A twist of twists” (2022)] Natalie Reznikov [为 Buss 等人撰写的社论《骨骼的三维分层组织：扭曲的扭曲"（2022 年］

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-10-30 DOI: 10.1016/j.yjsbx.2024.100116

引用次数: 0

Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STAB 成纤维细胞生长因子 2（FGF2-STAB）稳定形式的结构分析

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-10-24 DOI: 10.1016/j.yjsbx.2024.100112

Gabin de La Bourdonnaye , Martin Marek , Tereza Ghazalova , Jiri Damborsky , Petr Pachl , Jiri Brynda , Veronika Stepankova , Radka Chaloupkova

{"title":"Structural analysis of the stable form of fibroblast growth factor 2 – FGF2-STAB","authors":"Gabin de La Bourdonnaye , Martin Marek , Tereza Ghazalova , Jiri Damborsky , Petr Pachl , Jiri Brynda , Veronika Stepankova , Radka Chaloupkova","doi":"10.1016/j.yjsbx.2024.100112","DOIUrl":"10.1016/j.yjsbx.2024.100112","url":null,"abstract":"<div><div>Fibroblast growth factor 2 (FGF2) is a signaling protein that plays a significant role in tissue development and repair. FGF2 binds to fibroblast growth factor receptors (FGFRs) alongside its co-factor heparin, which protects FGF2 from degradation. The binding between FGF2 and FGFRs induces intracellular signaling pathways such as RAS-MAPK, PI3K-AKT, and STAT. FGF2 has strong potential for application in cell culturing, wound healing, and cosmetics but the potential is severely limited by its low protein stability. The thermostable variant FGF2-STAB was constructed by computer-assisted protein engineering to overcome the natural limitation of FGF2. Previously reported characterization of FGF2-STAB revealed an enhanced ability to induce MAP/ERK signaling while having a lower dependence on heparin when compared with FGF2-wt. Here we report the crystal structure of FGF2-STAB solved at 1.3 Å resolution. Protein stabilization is achieved by newly formed hydrophobic interactions, polar contacts, and one additional hydrogen bond. The overall structure of FGF2-STAB is similar to FGF2-wt and does not reveal information on the experimentally observed lower dependence on heparin. A noticeable difference in flexibility in the receptor binding region can explain the differences in signaling between FGF2-STAB and its wild-type counterpart. Our structural analysis provided molecular insights into the stabilization and unique biological properties of FGF2-STAB.</div></div>","PeriodicalId":17238,"journal":{"name":"Journal of Structural Biology: X","volume":"10 ","pages":"Article 100112"},"PeriodicalIF":3.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531009","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

Localization of albumin with correlative super resolution light- and electron microscopy in the kidney 利用相关超分辨率光镜和电子显微镜确定肾脏中白蛋白的位置

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-10-21 DOI: 10.1016/j.yjsbx.2024.100114

Alexandra N. Birtasu , Utz H. Ermel , Johanna V. Rahm , Anja Seybert , Benjamin Flottmann , Mike Heilemann , Florian Grahammer , Achilleas S. Frangakis

{"title":"Localization of albumin with correlative super resolution light- and electron microscopy in the kidney","authors":"Alexandra N. Birtasu , Utz H. Ermel , Johanna V. Rahm , Anja Seybert , Benjamin Flottmann , Mike Heilemann , Florian Grahammer , Achilleas S. Frangakis","doi":"10.1016/j.yjsbx.2024.100114","DOIUrl":"10.1016/j.yjsbx.2024.100114","url":null,"abstract":"<div><div>The functioning of vertebrate life relies on renal filtration of surplus fluid and elimination of low-molecular-weight waste products, while keeping serum proteins in the blood. In disease, however, there is leak of serum proteins and tracing them to identify the leaking position within tissue with a nanometer resolution poses a significant challenge. Correlative microscopy integrates the specificity of fluorescent protein labeling into high-resolution electron micrographs. Using chemical tagging of albumin with synthetic fluorophores we achieve protein-specific labeling that preserve their post-embedding fluorescence after high-pressure freezing and freeze-substitution of murine kidney tissue. Using advanced registration techniques for super-resolution correlative light and electron microscopy, we can localize the labeled albumin with a high precision in the x-y plane of electron micrographs and cartograph its distribution. Thereby we can quantify the albumin concentration and measure a linear reduction gradient across the kidney filtration barrier. Our study shows the feasibility of combining different microscopy contrasts for tracing fluorescently labeled protein markers with super resolution in various tissue samples and opens new perspectives for correlative imaging in volume electron microscopy.</div></div>","PeriodicalId":17238,"journal":{"name":"Journal of Structural Biology: X","volume":"10 ","pages":"Article 100114"},"PeriodicalIF":3.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142538214","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

Minimizing ice contamination during specimen preparation for cryo-soft X-ray tomography and cryo-electron tomography 尽量减少低温软 X 射线断层扫描和低温电子断层扫描标本制备过程中的冰污染

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-10-18 DOI: 10.1016/j.yjsbx.2024.100113

Chia-Chun Hsieh, Zi-Jing Lin, Lee-Jene Lai

{"title":"Minimizing ice contamination during specimen preparation for cryo-soft X-ray tomography and cryo-electron tomography","authors":"Chia-Chun Hsieh, Zi-Jing Lin, Lee-Jene Lai","doi":"10.1016/j.yjsbx.2024.100113","DOIUrl":"10.1016/j.yjsbx.2024.100113","url":null,"abstract":"<div><div>Cryo-soft X-ray tomography (cryo-SXT) is a newly developed technique for imaging 3D whole cells in nearly native states. Cryo-SXT users require the preparation of numerous cryo-sample grids to use the allocated beamtime to study cellular phenomena under various conditions. Therefore, it is important to promptly prepare cryo-sample grids as efficiently and carefully as possible to minimize ice contamination on the frozen sample grid. In this study, we designed a cryo-multi-grid-box storage system, which includes a shell, funnel holder, and multi-grid-box container. Our system not only increases the number of cryo-sample grids that can be temporarily stored but also reduces the frequency of cryo grid-box container transfers, thus decreasing the probability of forming ice on the grid. We have also applied this system to A549 cryo cell grid preparation. The correlative images from cryo-light microscopy and cryo-SXT showed that limited ice had formed on the grid when preparation was performed using our system. Additionally, 3D images of mitochondria with the lamellar shape of the cristae could be observed in our cryo-SXT results. Our cryo-multi-grid-box storage system can be used for cryo-SXT and cryo-electron tomography (cryo-ET) applications.</div></div>","PeriodicalId":17238,"journal":{"name":"Journal of Structural Biology: X","volume":"10 ","pages":"Article 100113"},"PeriodicalIF":3.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530489","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

Assessment of submicron bone tissue composition in plastic-embedded samples using optical photothermal infrared (O-PTIR) spectral imaging and machine learning 利用光学光热红外（O-PTIR）光谱成像和机器学习评估塑料包埋样本中的亚微米骨组织成分

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-10-09 DOI: 10.1016/j.yjsbx.2024.100111

Isha Dev , Sofia Mehmood , Nancy Pleshko , Iyad Obeid , William Querido

{"title":"Assessment of submicron bone tissue composition in plastic-embedded samples using optical photothermal infrared (O-PTIR) spectral imaging and machine learning","authors":"Isha Dev , Sofia Mehmood , Nancy Pleshko , Iyad Obeid , William Querido","doi":"10.1016/j.yjsbx.2024.100111","DOIUrl":"10.1016/j.yjsbx.2024.100111","url":null,"abstract":"<div><div>Understanding the composition of bone tissue at the submicron level is crucial to elucidate factors contributing to bone disease and fragility. Here, we introduce a novel approach utilizing optical photothermal infrared (O-PTIR) spectroscopy and imaging coupled with machine learning analysis to assess bone tissue composition at 500 nm spatial resolution. This approach was used to evaluate thick bone samples embedded in typical poly(methyl methacrylate) (PMMA) blocks, eliminating the need for cumbersome thin sectioning. We demonstrate the utility of O-PTIR imaging to assess the distribution of bone tissue mineral and protein, as well as to explore the structure-composition relationship surrounding microporosity at a spatial resolution unattainable by conventional infrared imaging modalities. Using bone samples from wildtype (WT) mice and from a mouse model of osteogenesis imperfecta (OIM), we further showcase the application of O-PTIR spectroscopy to quantify mineral content, crystallinity, and carbonate content in spatially defined regions across the cortical bone. Notably, we show that machine learning analysis using support vector machine (SVM) was successful in identifying bone phenotypes (typical in WT, fragile in OIM) based on input of spectral data, with over 86 % of samples correctly identified when using the collagen spectral range. Our findings highlight the potential of O-PTIR spectroscopy and imaging as valuable tools for exploring bone submicron composition.</div></div>","PeriodicalId":17238,"journal":{"name":"Journal of Structural Biology: X","volume":"10 ","pages":"Article 100111"},"PeriodicalIF":3.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530909","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

Conformational variability in the D2 loop of Plasmodium Apical Membrane antigen 1 疟原虫顶膜抗原 1 D2 环的构象变异性

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-09-10 DOI: 10.1016/j.yjsbx.2024.100110

Frederick A. Saul , Brigitte Vulliez-Le Normand , Alexander Boes , Holger Spiegel , Clemens H.M. Kocken , Bart W. Faber , Graham A. Bentley

{"title":"Conformational variability in the D2 loop of Plasmodium Apical Membrane antigen 1","authors":"Frederick A. Saul , Brigitte Vulliez-Le Normand , Alexander Boes , Holger Spiegel , Clemens H.M. Kocken , Bart W. Faber , Graham A. Bentley","doi":"10.1016/j.yjsbx.2024.100110","DOIUrl":"10.1016/j.yjsbx.2024.100110","url":null,"abstract":"<div><p>Apical Membrane Antigen 1 (AMA1) plays a vital role in the invasion of the host erythrocyte by the malaria parasite, <em>Plasmodium</em>. It is thus an important target for vaccine and anti-malaria therapeutic strategies that block the invasion process. AMA1, present on the surface of the parasite, interacts with RON2, a component of the parasite’s rhoptry neck (RON) protein complex, which is transferred to the erythrocyte membrane during invasion. The D2 loop of AMA1 plays an essential role in invasion as it partially covers the RON2-binding site and must therefore be displaced for invasion to proceed. Several structural studies have shown that the D2 loop is very mobile, a property that is probably important for the function of AMA1. Here we present three crystal structures of AMA1 from <em>P. falciparum</em> (strains 3D7 and FVO) and <em>P. vivax</em> (strain Sal1), in which the D2 loop could be largely traced in the electron density maps. The D2 loop of PfAMA1-FVO and PvAMA1 (as a complex with a monoclonal antibody Fab) has a conformation previously noted in the <em>P. knowlesi</em> AMA1 structure. The D2 loop of PfAMA1-3D7, however, reveals a novel conformation. We analyse the conformational variability of the D2 loop in these structures, together with those previously reported. Three different conformations can be distinguished, all of which are highly helical and show some similarity in their secondary structure organisation. We discuss the significance of these observations in the light of the flexible nature of the D2 loop and its role in AMA1 function.</p></div>","PeriodicalId":17238,"journal":{"name":"Journal of Structural Biology: X","volume":"10 ","pages":"Article 100110"},"PeriodicalIF":3.5,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590152424000151/pdfft?md5=18146cbe19a02e66f922067a1ea42cae&pid=1-s2.0-S2590152424000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243547","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 of SARS-CoV-2 MTase nsp14 with the inhibitor STM957 reveals inhibition mechanism that is shared with a poxviral MTase VP39 SARS-CoV-2 MT 酶 nsp14 与抑制剂 STM957 的结构揭示了与痘病毒 MT 酶 VP39 共享的抑制机制

IF 3.5

Journal of Structural Biology: X Pub Date : 2024-07-29 DOI: 10.1016/j.yjsbx.2024.100109

Eva Zilecka, Martin Klima, Milan Stefek, Milan Dejmek, Radim Nencka, Evzen Boura

{"title":"Structure of SARS-CoV-2 MTase nsp14 with the inhibitor STM957 reveals inhibition mechanism that is shared with a poxviral MTase VP39","authors":"Eva Zilecka, Martin Klima, Milan Stefek, Milan Dejmek, Radim Nencka, Evzen Boura","doi":"10.1016/j.yjsbx.2024.100109","DOIUrl":"10.1016/j.yjsbx.2024.100109","url":null,"abstract":"<div><p>Nsp14 is an RNA methyltransferase (MTase) encoded by all coronaviruses. In fact, many viral families, including DNA viruses, encode MTases that catalyze the methylation of the RNA precap structure, resulting in fully capped viral RNA. This capping is crucial for efficient viral RNA translation, stability, and immune evasion. Our previous research identified nsp14 inhibitors based on the chemical scaffold of its methyl donor − the S-adenosyl methionine (SAM) − featuring a modified adenine base and a substituted arylsulfonamide. However, the binding mode of these inhibitors was based only on docking experiments. To uncover atomic details of nsp14 inhibition we solved the crystal structure of nsp14 bound to STM957. The structure revealed the atomic details of nsp14 inhibition such that the 7-deaza-adenine moiety of STM957 forms specific interactions with Tyr368, Ala353, and Phe367, while the arylsulfonamide moiety engages with Asn388 and Phe506. The large aromatic substituent at the 7-deaza position displaces a network of water molecules near the adenine base. Surprisingly, this was recently observed in the case of an unrelated monkeypox MTase VP39, where the 7-deaza modified SAH analogs also displaced water molecules from the vicinity of the active site.</p></div>","PeriodicalId":17238,"journal":{"name":"Journal of Structural Biology: X","volume":"10 ","pages":"Article 100109"},"PeriodicalIF":3.5,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259015242400014X/pdfft?md5=adc7af4fba68360ac9d28aa0d253354d&pid=1-s2.0-S259015242400014X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141962088","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