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De novo design of semisynthetic conduction pores 半合成导电孔的全新设计
Nature structural & molecular biology Pub Date : 2026-09-21 DOI: 10.1038/s41594-026-01881-w
Lee Schnaider, A. Katherine Hatstat, Alistair J. Scott, Sophia K. Tan, Richard G. Hambley, William M. Dawson, Rhys C. Griffiths, Rian C. Kormos, Arthur A. Melo, Eric Tse, Nicholas F. Polizzi, E. Jayne Wallace, Gregory E. Merz, William F. DeGrado
{"title":"De novo design of semisynthetic conduction pores","authors":"Lee Schnaider, A. Katherine Hatstat, Alistair J. Scott, Sophia K. Tan, Richard G. Hambley, William M. Dawson, Rhys C. Griffiths, Rian C. Kormos, Arthur A. Melo, Eric Tse, Nicholas F. Polizzi, E. Jayne Wallace, Gregory E. Merz, William F. DeGrado","doi":"10.1038/s41594-026-01881-w","DOIUrl":"https://doi.org/10.1038/s41594-026-01881-w","url":null,"abstract":"Protein pores used for molecular sensing are generally assembled from large, multi-subunit natural proteins. Their ion conductance, and thus performance in sensing applications, depends on lumen geometry and chemistry. Here rather than designing a new pore or relying only on mutations to a natural scaffold, we show that installing additional de novo subunits to native protein pore complexes enables large-scale architectural changes. We design de novo proteins that integrate seamlessly with CsgG, a pore widely used in sensing applications, to form 18-subunit, 315-kilodalton semisynthetic conduction pores. This required designing within a confined, nonuniform pore under ninefold symmetry and maintaining an open conducting lumen with a stable, low-noise baseline current. The complexes exhibit distinct current–voltage responses relative to the native pore, including clear rectification, while cryo-electron microscopy confirms the designed lumen architecture, establishing a strategy for modifying existing nano-assemblies with designed protein components under stringent symmetry and structural constraints.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149010473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Author Correction: Structural basis of the histone ubiquitination read-write mechanism of RYBP-PRC1. 作者更正：RYBP-PRC1组蛋白泛素化读写机制的结构基础。
Nature structural & molecular biology Pub Date : 2025-08-27 DOI: 10.1038/s41594-025-01674-7
Maria Ciapponi,Elena Karlukova,Sven Schkölziger,Christian Benda,Jürg Müller
{"title":"Author Correction: Structural basis of the histone ubiquitination read-write mechanism of RYBP-PRC1.","authors":"Maria Ciapponi,Elena Karlukova,Sven Schkölziger,Christian Benda,Jürg Müller","doi":"10.1038/s41594-025-01674-7","DOIUrl":"https://doi.org/10.1038/s41594-025-01674-7","url":null,"abstract":"","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Epitranscriptome regulation. 上皮转录组调控。
Nature structural & molecular biology Pub Date : 2018-09-28 DOI: 10.1038/s41594-018-0140-7
Dan Dominissini, Gideon Rechavi
{"title":"Epitranscriptome regulation.","authors":"Dan Dominissini, Gideon Rechavi","doi":"10.1038/s41594-018-0140-7","DOIUrl":"10.1038/s41594-018-0140-7","url":null,"abstract":"","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2018-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36535441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation. 调控片段的亚基间捕获是CaMKII协同激活的一个组成部分。
Nature structural & molecular biology Pub Date : 2010-03-01 Epub Date: 2010-02-07 DOI: 10.1038/nsmb.1751
Luke H Chao, Patricia Pellicena, Sebastian Deindl, Lauren A Barclay, Howard Schulman, John Kuriyan
{"title":"Intersubunit capture of regulatory segments is a component of cooperative CaMKII activation.","authors":"Luke H Chao, Patricia Pellicena, Sebastian Deindl, Lauren A Barclay, Howard Schulman, John Kuriyan","doi":"10.1038/nsmb.1751","DOIUrl":"10.1038/nsmb.1751","url":null,"abstract":"<p><p>The dodecameric holoenzyme of calcium-calmodulin-dependent protein kinase II (CaMKII) responds to high-frequency Ca(2+) pulses to become Ca(2+) independent. A simple coincidence-detector model for Ca(2+)-frequency dependency assumes noncooperative activation of kinase domains. We show that activation of CaMKII by Ca(2+)-calmodulin is cooperative, with a Hill coefficient of approximately 3.0, implying sequential kinase-domain activation beyond dimeric units. We present data for a model in which cooperative activation includes the intersubunit 'capture' of regulatory segments. Such a capture interaction is seen in a crystal structure that shows extensive contacts between the regulatory segment of one kinase and the catalytic domain of another. These interactions are mimicked by a natural inhibitor of CaMKII. Our results show that a simple coincidence-detection model cannot be operative and point to the importance of kinetic dissection of the frequency-response mechanism in future experiments.</p>","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"17 3","pages":"264-72"},"PeriodicalIF":0.0,"publicationDate":"2010-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2855215/pdf/nihms-188695.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9338579","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
Domain structure of separase and its binding to securin as determined by EM. 分离酶的结构域结构及其与securin的结合。
Nature structural & molecular biology Pub Date : 2005-06-01 Epub Date: 2005-05-08 DOI: 10.1038/nsmb935
Hector Viadiu, Olaf Stemmann, Marc W Kirschner, Thomas Walz
{"title":"Domain structure of separase and its binding to securin as determined by EM.","authors":"Hector Viadiu,&nbsp;Olaf Stemmann,&nbsp;Marc W Kirschner,&nbsp;Thomas Walz","doi":"10.1038/nsmb935","DOIUrl":"https://doi.org/10.1038/nsmb935","url":null,"abstract":"<p><p>After the degradation of its inhibitor securin, separase initiates chromosome segregation during the metaphase-to-anaphase transition by cleaving cohesin. Here we present a density map at a resolution of 25 A of negatively stained separase-securin complex. Based on labeling data and sequence analysis, we propose a model for the structure of separase, consisting of 26 ARM repeats, an unstructured region of 280 residues and two caspase-like domains, with securin binding to the ARM repeats.</p>","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"12 6","pages":"552-3"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/nsmb935","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25271368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 51
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