Structure最新文献

{"title":"FakET: Simulating cryo-electron tomograms with neural style transfer","authors":"Pavol Harar, Lukas Herrmann, Philipp Grohs, David Haselbach","doi":"10.1016/j.str.2025.01.020","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.020","url":null,"abstract":"In cryo-electron microscopy, accurate particle localization and classification are imperative. Recent deep learning solutions, though successful, require extensive training datasets. The protracted generation time of physics-based models, often employed to produce these datasets, limits their broad applicability. We introduce FakET, a method based on neural style transfer, capable of simulating the forward operator of any cryo transmission electron microscope. It can be used to adapt a synthetic training dataset according to reference data producing high-quality simulated micrographs or tilt-series. To assess the quality of our generated data, we used it to train a state-of-the-art localization and classification architecture and compared its performance with a counterpart trained on benchmark data. Remarkably, our technique matches the performance, boosts data generation speed <span><span style=\"\"></span><span data-mathml='<math xmlns=\"http://www.w3.org/1998/Math/MathML\"><mrow is=\"true\"><mn is=\"true\">750</mn><mo linebreak=\"goodbreak\" linebreakstyle=\"after\" is=\"true\">×</mo></mrow></math>' role=\"presentation\" style=\"font-size: 90%; display: inline-block; position: relative;\" tabindex=\"0\"><svg aria-hidden=\"true\" focusable=\"false\" height=\"1.971ex\" role=\"img\" style=\"vertical-align: -0.235ex;\" viewbox=\"0 -747.2 2280 848.5\" width=\"5.296ex\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g fill=\"currentColor\" stroke=\"currentColor\" stroke-width=\"0\" transform=\"matrix(1 0 0 -1 0 0)\"><g is=\"true\"><g is=\"true\"><use xlink:href=\"#MJMAIN-37\"></use><use x=\"500\" xlink:href=\"#MJMAIN-35\" y=\"0\"></use><use x=\"1001\" xlink:href=\"#MJMAIN-30\" y=\"0\"></use></g><g is=\"true\" transform=\"translate(1501,0)\"><use xlink:href=\"#MJMAIN-D7\"></use></g></g></g></svg><span role=\"presentation\"><math xmlns=\"http://www.w3.org/1998/Math/MathML\"><mrow is=\"true\"><mn is=\"true\">750</mn><mo is=\"true\" linebreak=\"goodbreak\" linebreakstyle=\"after\">×</mo></mrow></math></span></span><script type=\"math/mml\"><math><mrow is=\"true\"><mn is=\"true\">750</mn><mo linebreak=\"goodbreak\" linebreakstyle=\"after\" is=\"true\">×</mo></mrow></math></script></span>, uses <span><span style=\"\"></span><span data-mathml='<math xmlns=\"http://www.w3.org/1998/Math/MathML\"><mrow is=\"true\"><mn is=\"true\">33</mn><mo linebreak=\"goodbreak\" linebreakstyle=\"after\" is=\"true\">×</mo></mrow></math>' role=\"presentation\" style=\"font-size: 90%; display: inline-block; position: relative;\" tabindex=\"0\"><svg aria-hidden=\"true\" focusable=\"false\" height=\"1.971ex\" role=\"img\" style=\"vertical-align: -0.235ex;\" viewbox=\"0 -747.2 1779.5 848.5\" width=\"4.133ex\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"><g fill=\"currentColor\" stroke=\"currentColor\" stroke-width=\"0\" transform=\"matrix(1 0 0 -1 0 0)\"><g is=\"true\"><g is=\"true\"><use xlink:href=\"#MJMAIN-33\"></use><use x=\"500\" xlink:href=\"#MJMAIN-33\" y=\"0\"></use></g><g is=\"true\" transform=\"translate(1001","PeriodicalId":22168,"journal":{"name":"Structure","volume":"129 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unique mechanisms to increase structural stability and enhance antigen binding in nanobodies","authors":"Natalia E. Ketaren, Peter C. Fridy, Vladimir Malashkevich, Tanmoy Sanyal, Marc Brillantes, Mary K. Thompson, Deena A. Oren, Jeffrey B. Bonanno, Andrej Šali, Steven C. Almo, Brian T. Chait, Michael P. Rout","doi":"10.1016/j.str.2025.01.019","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.019","url":null,"abstract":"Nanobodies are single domain antibody variants proving themselves to be compelling tools for research, disease diagnostics, and as therapeutics targeting a myriad of disease agents. However, despite this potential, their mechanisms of paratope presentation and structural stabilization have not been fully explored. Here, we show that unlike monoclonal antibodies, a nanobody repertoire maximizes sampling of an antigen surface by binding a single antigen in at least three different orientations, which are correlated with their paratope composition. Structure-guided reengineering of several nanobodies reveals that a single point mutation within the paratope or a highly conserved region of a nanobody’s framework 3 (FR3) can markedly improve antigen affinity, nanobody stability, or both. Conversely, we show the negative impact on antigen affinity when “over-stabilizing” nanobodies. Collectively our results provide a universal strategy to tune a nanobody’s affinity by modifying specific residues that can readily be applied to guide nanobody optimization and functionalization.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"128 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic integration of feature- and template-based methods improves the prediction of conformational B cell epitopes","authors":"Yueyue Shen, Zheng Jiang, Rong Liu","doi":"10.1016/j.str.2025.01.018","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.018","url":null,"abstract":"The accurate prediction of conformational epitopes promotes our understanding of antigen-antibody interactions. All existing algorithms depend on a feature-based strategy, which limits their performance. A template-based strategy can provide complementary information, and the interplay between these two strategies could improve the prediction of epitopes. Here, we present DynaBCE, a dynamic ensemble algorithm to effectively identify conformational B cell epitopes (BCEs). Using novel handcrafted structural descriptors and embeddings from protein language models, we developed machine learning and deep learning modules based on boosting algorithms and geometric graph neural networks, respectively. Furthermore, we built a template module by leveraging known structural template information and transformer-based algorithms to capture binding signatures. Finally, we integrated the three modules using a dynamic weighting approach to maximize the strength of each module for different samples. DynaBCE achieved promising results for both native and predicted structures and outperformed previous methods as demonstrated in various evaluation scenarios.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"28 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective deuteration of an RNA:RNA complex for structural analysis using small-angle scattering","authors":"Aldrex Munsayac, Wellington C. Leite, Jesse B. Hopkins, Ian Hall, Hugh M. O’Neill, Sarah C. Keane","doi":"10.1016/j.str.2025.01.017","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.017","url":null,"abstract":"The structures of RNA:RNA complexes regulate many biological processes. Despite their importance, protein-free RNA:RNA complexes represent a tiny fraction of experimentally determined structures. Here, we describe a joint small-angle X-ray and neutron scattering (SAXS/SANS) approach to structurally interrogate conformational changes in a model RNA:RNA complex. Using SAXS, we measured the solution structures of the individual RNAs and of the overall RNA:RNA complex. With SANS, we demonstrate, as a proof of principle, that isotope labeling and contrast matching (CM) can be combined to probe the bound state structure of an RNA within a selectively deuterated RNA:RNA complex. Furthermore, we show that experimental scattering data can validate and improve predicted AlphaFold 3 RNA:RNA complex structures to reflect its solution structure. Our work demonstrates that <em>in silico</em> modeling, SAXS, and CM-SANS can be used in concert to directly analyze conformational changes within RNAs when in complex, enhancing our understanding of RNA structure in functional assemblies.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"13 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcription termination—Some like it hot","authors":"Kristine Bourke Arnvig, Finn Werner","doi":"10.1016/j.str.2025.01.016","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.016","url":null,"abstract":"In this issue of <em>Structure</em>, Dikunova et al.<span><span>¹</span></span> report the structure of the trimeric torpedo complex, the key factor responsible for transcription termination by RNA polymerase II R(NAPII) at the end of protein-encoding genes. The comparison between meso- and thermophilic torpedoes provides intriguing insights into thermal adaptions and mechanisms of termination.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"12 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CryoVIA: An image analysis toolkit for the quantification of membrane structures from cryo-EM micrographs","authors":"Philipp Schönnenbeck, Benedikt Junglas, Carsten Sachse","doi":"10.1016/j.str.2025.01.013","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.013","url":null,"abstract":"Imaging of lipid structures and associated protein complexes using cryoelectron microscopy (cryo-EM) is a common visualization and structure determination technique. The quantitative analysis of the membrane structures, however, is not routine and time consuming in particular when large amounts of data are involved. Here, we introduce the automated image-processing software <em>cryo-vesicle image analyzer</em> (CryoVIA) that parametrizes lipid structures of large datasets from cryo-EM images. This toolkit combines segmentation, structure identification with methods to automatically perform a large-scale data analysis of local and global membrane properties such as bilayer thickness, size, and curvature including membrane shape classifications. We included analyses of exemplary datasets of different lipid compositions and protein-induced lipid changes through an endosomal sorting complexes required for transport III (ESCRT-III) membrane remodeling protein. The toolkit opens new possibilities to systematically study structural properties of membrane structures and their modifications from cryo-EM images.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"42 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Illuminating cholesterol-mTORC1 signaling: LYCHOS in focus","authors":"Hijai R. Shin, Roberto Zoncu","doi":"10.1016/j.str.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.009","url":null,"abstract":"In a recent issue of <em>Nature</em>, Bayly-Jones et al.<span><span>¹</span></span> report the first cryoelectron microscopy (cryo-EM) structure of the lysosomal transmembrane protein LYCHOS, which mediates cholesterol sensing by mTORC1. LYCHOS forms a homodimer, with cholesterol engagement at the transporter-GPCR domain interface, coupled to auxin binding at the transporter-like domain, suggesting multi-domain coordination as critical for cholesterol sensing.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"13 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Anti-TB Structural Center at ShanghaiTech University","authors":"Haitao Yang, Lu Zhang, Quan Wang, Jun Li, Xiuna Yang, Yan Gao, Bing Zhang","doi":"10.1016/j.str.2025.01.006","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.006","url":null,"abstract":"In this Voices article, we introduce seven group leaders from the Anti-TB Structure Center (ATSC) in Shanghai, which was opened in 2020. The scientists at ATSC closely collaborate with the goal of identifying new drug targets and developing novel therapeutics against tuberculosis, COVID-19, and other infectious diseases.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"137 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial sodium channels assemble in an orderly manner: Biology does not play dice","authors":"Sarah Pellizzari, Erhu Cao","doi":"10.1016/j.str.2025.01.015","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.015","url":null,"abstract":"In this issue of <em>Structure</em>, Houser et al.<span><span>¹</span></span> report cryoelectron microscopy (cryo-EM) structures of two atypical forms of the heterotrimeric epithelial sodium channel (ENaC) in which either a δ or a β subunit assembles with one β and one γ subunit. These structures shed light on the molecular principles that govern the assembly of distinct ENaC trimers.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"31 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanosensitive channel YbiO has a conductance equivalent to the largest gated-pore","authors":"Benjamin J. Lane, Mariangela Dionysopoulou, Nana Yan, Jonathan D. Lippiat, Stephen P. Muench, Christos Pliotas","doi":"10.1016/j.str.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.str.2025.01.014","url":null,"abstract":"Bacterial mechanosensitive channels are divided into large (MscL) and small (MscS-like) conductance families. The function of MscS and MscL is to protect cells against osmotic shock by acting as pressure safety valves. Within the MscS-like family, <em>E</em>. <em>coli</em> encodes much larger channels, such as YbiO, MscK, and MscM, but their physiological role remains unclear. Compared to MscL their conductances are reported as 3–10 times lower. We show that YbiO can achieve a conductance of ∼3 nS, and an equivalent pore opening of &gt; 25 Å in diameter, equaling the known largest gated pore, MscL. We determine a cryoelectron microscopy (cryo-EM) structure of YbiO in a sub-open conformation, demonstrating the existence of multiple substates. One substate is consistent with the pore opening extent of our structure and the other matches states previously thought to resemble full openings. Our findings demonstrate surprising capabilities, hinting at new physiological roles for YbiO and potentially other MscS-like channels.","PeriodicalId":22168,"journal":{"name":"Structure","volume":"62 1","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}