Nature Structural & Molecular Biology最新文献_第10页

Mechanisms of transcription and RNA processing 转录和 RNA 处理机制

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-14 DOI: 10.1038/s41594-024-01312-8

Lori A. Passmore, Suyang Zhang

引用次数: 0

Decoding branch points and unlocking splicing secrets 解码分支点，揭开剪接的秘密

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-13 DOI: 10.1038/s41594-024-01308-4

Sara R. Downs, Bec Grace, Jeffrey A. Pleiss

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Computational design of non-porous pH-responsive antibody nanoparticles 无孔 pH 值响应型抗体纳米粒子的计算设计

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-09 DOI: 10.1038/s41594-024-01288-5

Erin C. Yang, Robby Divine, Marcos C. Miranda, Andrew J. Borst, Will Sheffler, Jason Z. Zhang, Justin Decarreau, Amijai Saragovi, Mohamad Abedi, Nicolas Goldbach, Maggie Ahlrichs, Craig Dobbins, Alexis Hand, Suna Cheng, Mila Lamb, Paul M. Levine, Sidney Chan, Rebecca Skotheim, Jorge Fallas, George Ueda, Joshua Lubner, Masaharu Somiya, Alena Khmelinskaia, Neil P. King, David Baker

{"title":"Computational design of non-porous pH-responsive antibody nanoparticles","authors":"Erin C. Yang, Robby Divine, Marcos C. Miranda, Andrew J. Borst, Will Sheffler, Jason Z. Zhang, Justin Decarreau, Amijai Saragovi, Mohamad Abedi, Nicolas Goldbach, Maggie Ahlrichs, Craig Dobbins, Alexis Hand, Suna Cheng, Mila Lamb, Paul M. Levine, Sidney Chan, Rebecca Skotheim, Jorge Fallas, George Ueda, Joshua Lubner, Masaharu Somiya, Alena Khmelinskaia, Neil P. King, David Baker","doi":"10.1038/s41594-024-01288-5","DOIUrl":"10.1038/s41594-024-01288-5","url":null,"abstract":"Programming protein nanomaterials to respond to changes in environmental conditions is a current challenge for protein design and is important for targeted delivery of biologics. Here we describe the design of octahedral non-porous nanoparticles with a targeting antibody on the two-fold symmetry axis, a designed trimer programmed to disassemble below a tunable pH transition point on the three-fold axis, and a designed tetramer on the four-fold symmetry axis. Designed non-covalent interfaces guide cooperative nanoparticle assembly from independently purified components, and a cryo-EM density map closely matches the computational design model. The designed nanoparticles can package protein and nucleic acid payloads, are endocytosed following antibody-mediated targeting of cell surface receptors, and undergo tunable pH-dependent disassembly at pH values ranging between 5.9 and 6.7. The ability to incorporate almost any antibody into a non-porous pH-dependent nanoparticle opens up new routes to antibody-directed targeted delivery. Designed novel protein nanoparticle technology integrates antibody targeting and responds to changes in environmental conditions to release protected molecular cargoes, opening new applications for precision medicine.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 9","pages":"1404-1412"},"PeriodicalIF":12.5,"publicationDate":"2024-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01288-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140895556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Custom protein nanoparticles for targeted drug delivery 用于靶向给药的定制蛋白质纳米颗粒

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-09 DOI: 10.1038/s41594-024-01289-4

引用次数: 0

Cryo-EM structure of the Rev1–Polζ holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis Rev1-Polζ 整体复合物的低温电子显微镜结构揭示了它们在转座子 DNA 合成中的合作机制

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-08 DOI: 10.1038/s41594-024-01302-w

Radhika Malik, Robert E. Johnson, Iban Ubarretxena-Belandia, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

{"title":"Cryo-EM structure of the Rev1–Polζ holocomplex reveals the mechanism of their cooperativity in translesion DNA synthesis","authors":"Radhika Malik, Robert E. Johnson, Iban Ubarretxena-Belandia, Louise Prakash, Satya Prakash, Aneel K. Aggarwal","doi":"10.1038/s41594-024-01302-w","DOIUrl":"10.1038/s41594-024-01302-w","url":null,"abstract":"Rev1–Polζ-dependent translesion synthesis (TLS) of DNA is crucial for maintaining genome integrity. To elucidate the mechanism by which the two polymerases cooperate in TLS, we determined the cryogenic electron microscopic structure of the Saccharomyces cerevisiae Rev1–Polζ holocomplex in the act of DNA synthesis (3.53 Å). We discovered that a composite N-helix-BRCT module in Rev1 is the keystone of Rev1–Polζ cooperativity, interacting directly with the DNA template–primer and with the Rev3 catalytic subunit of Polζ. The module is positioned akin to the polymerase-associated domain in Y-family TLS polymerases and is set ideally to interact with PCNA. We delineate the full extent of interactions that the carboxy-terminal domain of Rev1 makes with Polζ and identify potential new druggable sites to suppress chemoresistance from first-line chemotherapeutics. Collectively, our results provide fundamental new insights into the mechanism of cooperativity between Rev1 and Polζ in TLS. The authors elucidate by cryo-EM the mechanism by which DNA polymerases Rev1 and Polζ cooperate in translesion DNA synthesis.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 9","pages":"1394-1403"},"PeriodicalIF":12.5,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140881287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Target-based discovery of a broad-spectrum flukicide 基于靶标发现广谱杀卵剂

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-07 DOI: 10.1038/s41594-024-01298-3

Daniel J. Sprague, Sang-Kyu Park, Svenja Gramberg, Lisa Bauer, Claudia M. Rohr, Evgeny G. Chulkov, Emery Smith, Louis Scampavia, Timothy P. Spicer, Simone Haeberlein, Jonathan S. Marchant

{"title":"Target-based discovery of a broad-spectrum flukicide","authors":"Daniel J. Sprague, Sang-Kyu Park, Svenja Gramberg, Lisa Bauer, Claudia M. Rohr, Evgeny G. Chulkov, Emery Smith, Louis Scampavia, Timothy P. Spicer, Simone Haeberlein, Jonathan S. Marchant","doi":"10.1038/s41594-024-01298-3","DOIUrl":"10.1038/s41594-024-01298-3","url":null,"abstract":"Diseases caused by parasitic flatworms impart a considerable healthcare burden worldwide. Many of these diseases—for example, the parasitic blood fluke infection schistosomiasis—are treated with the drug praziquantel (PZQ). However, PZQ is ineffective against disease caused by liver flukes from the genus Fasciola because of a single amino acid change within the target of PZQ, a transient receptor potential ion channel in the melastatin family (TRPMPZQ), in Fasciola species. Here, we identify benzamidoquinazolinone analogs that are active against Fasciola TRPMPZQ. Structure–activity studies define an optimized ligand (BZQ) that caused protracted paralysis and tegumental damage to these liver flukes. BZQ also retained activity against Schistosoma mansoni comparable to PZQ and was active against TRPMPZQ orthologs in all profiled species of parasitic fluke. This broad-spectrum activity manifests as BZQ adopts a pose within the binding pocket of TRPMPZQ that is dependent on a ubiquitously conserved residue. BZQ therefore acts as a universal activator of trematode TRPMPZQ and a first-in-class, broad-spectrum flukicide. The authors uncovered an antiparasitic molecule that exhibits broad-spectrum activity against parasitic flukes through engagement of a recently discovered transient receptor potential ion channel.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 9","pages":"1386-1393"},"PeriodicalIF":12.5,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Illuminating cortactin structure and function at actin filament branches 阐明肌动蛋白丝分支上的皮质联系蛋白结构和功能

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-07 DOI: 10.1038/s41594-024-01297-4

Klemens Rottner, Peter Bieling

引用次数: 0

The risky business of ADP-ribosylating telomeric DNA ADP-核糖基化端粒 DNA 的风险业务

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-07 DOI: 10.1038/s41594-024-01285-8

Ylli Doksani, Francisca Lottersberger

引用次数: 0

Deregulated DNA ADP-ribosylation impairs telomere replication DNA ADP-核糖基化失调会损害端粒复制

IF 16.8 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-07 DOI: 10.1038/s41594-024-01279-6

Anne R. Wondisford, Junyeop Lee, Robert Lu, Marion Schuller, Josephine Groslambert, Ragini Bhargava, Sandra Schamus-Haynes, Leyneir C. Cespedes, Patricia L. Opresko, Hilda A. Pickett, Jaewon Min, Ivan Ahel, Roderick J. O’Sullivan

{"title":"Deregulated DNA ADP-ribosylation impairs telomere replication","authors":"Anne R. Wondisford, Junyeop Lee, Robert Lu, Marion Schuller, Josephine Groslambert, Ragini Bhargava, Sandra Schamus-Haynes, Leyneir C. Cespedes, Patricia L. Opresko, Hilda A. Pickett, Jaewon Min, Ivan Ahel, Roderick J. O’Sullivan","doi":"10.1038/s41594-024-01279-6","DOIUrl":"10.1038/s41594-024-01279-6","url":null,"abstract":"The recognition that DNA can be ADP ribosylated provides an unexpected regulatory level of how ADP-ribosylation contributes to genome stability, epigenetics and immunity. Yet, it remains unknown whether DNA ADP-ribosylation (DNA-ADPr) promotes genome stability and how it is regulated. Here, we show that telomeres are subject to DNA-ADPr catalyzed by PARP1 and removed by TARG1. Mechanistically, we show that DNA-ADPr is coupled to lagging telomere DNA strand synthesis, forming at single-stranded DNA present at unligated Okazaki fragments and on the 3′ single-stranded telomere overhang. Persistent DNA-linked ADPr, due to TARG1 deficiency, eventually leads to telomere shortening. Furthermore, using the bacterial DNA ADP-ribosyl-transferase toxin to modify DNA at telomeres directly, we demonstrate that unhydrolyzed DNA-linked ADP-ribose compromises telomere replication and telomere integrity. Thus, by identifying telomeres as chromosomal targets of PARP1 and TARG1-regulated DNA-ADPr, whose deregulation compromises telomere replication and integrity, our study highlights and establishes the critical importance of controlling DNA-ADPr turnover for sustained genome stability. Telomeres are endogenous cellular targets of DNA ADP-ribosylation (DNA-ADPr). TARG1-regulated DNA-ADPr is coupled to lagging telomere DNA strand synthesis, and persistent DNA-ADPr, due to TARG1 deficiency, leads to telomere shortening and fragility.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 5","pages":"791-800"},"PeriodicalIF":16.8,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01279-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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

Cryo-EM structure reveals how SID-1 recognizes dsRNA that initiates systemic RNAi 低温电子显微镜结构揭示了 SID-1 如何识别启动系统性 RNAi 的 dsRNA

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-05-03 DOI: 10.1038/s41594-024-01277-8

引用次数: 0