Nature structural & molecular biology最新文献_第5页

Structural insight into synergistic activation of human 3-methylcrotonyl-CoA carboxylase 从结构上洞察人类 3-甲基巴豆酰-CoA羧化酶的协同激活作用

Nature structural & molecular biology Pub Date : 2024-09-02 DOI: 10.1038/s41594-024-01379-3

Jiayue Su, Xuyang Tian, Hang Cheng, Desheng Liu, Ziyi Wang, Shan Sun, Hong-Wei Wang, Sen-Fang Sui

引用次数: 0

Structural basis for lipid transfer by the ATG2A–ATG9A complex ATG2A-ATG9A 复合物脂质转移的结构基础

Nature structural & molecular biology Pub Date : 2024-08-22 DOI: 10.1038/s41594-024-01376-6

Yang Wang, Selma Dahmane, Rujuan Ti, Xinyi Mai, Lizhe Zhu, Lars-Anders Carlson, Goran Stjepanovic

{"title":"Structural basis for lipid transfer by the ATG2A–ATG9A complex","authors":"Yang Wang, Selma Dahmane, Rujuan Ti, Xinyi Mai, Lizhe Zhu, Lars-Anders Carlson, Goran Stjepanovic","doi":"10.1038/s41594-024-01376-6","DOIUrl":"https://doi.org/10.1038/s41594-024-01376-6","url":null,"abstract":"Autophagy is characterized by the formation of double-membrane vesicles called autophagosomes. Autophagy-related proteins (ATGs) 2A and 9A have an essential role in autophagy by mediating lipid transfer and re-equilibration between membranes for autophagosome formation. Here we report the cryo-electron microscopy structures of human ATG2A in complex with WD-repeat protein interacting with phosphoinositides 4 (WIPI4) at 3.2 Å and the ATG2A–WIPI4–ATG9A complex at 7 Å global resolution. On the basis of molecular dynamics simulations, we propose a mechanism of lipid extraction from the donor membranes. Our analysis revealed 3:1 stoichiometry of the ATG9A–ATG2A complex, directly aligning the ATG9A lateral pore with ATG2A lipid transfer cavity, and an interaction of the ATG9A trimer with both the N-terminal and the C-terminal tip of rod-shaped ATG2A. Cryo-electron tomography of ATG2A liposome-binding states showed that ATG2A tethers lipid vesicles at different orientations. In summary, this study provides a molecular basis for the growth of the phagophore membrane and lends structural insights into spatially coupled lipid transport and re-equilibration during autophagosome formation.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142021861","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

Structural plasticity of bacterial ESCRT-III protein PspA in higher-order assemblies 细菌 ESCRT-III 蛋白 PspA 在高阶组装中的结构可塑性

Nature structural & molecular biology Pub Date : 2024-08-16 DOI: 10.1038/s41594-024-01359-7

Benedikt Junglas, Esther Hudina, Philipp Schönnenbeck, Ilona Ritter, Anja Heddier, Beatrix Santiago-Schübel, Pitter F. Huesgen, Dirk Schneider, Carsten Sachse

{"title":"Structural plasticity of bacterial ESCRT-III protein PspA in higher-order assemblies","authors":"Benedikt Junglas, Esther Hudina, Philipp Schönnenbeck, Ilona Ritter, Anja Heddier, Beatrix Santiago-Schübel, Pitter F. Huesgen, Dirk Schneider, Carsten Sachse","doi":"10.1038/s41594-024-01359-7","DOIUrl":"https://doi.org/10.1038/s41594-024-01359-7","url":null,"abstract":"Eukaryotic members of the endosome sorting complex required for transport-III (ESCRT-III) family have been shown to form diverse higher-order assemblies. The bacterial phage shock protein A (PspA) has been identified as a member of the ESCRT-III superfamily, and PspA homo-oligomerizes to form rod-shaped assemblies. As observed for eukaryotic ESCRT-III, PspA forms tubular assemblies of varying diameters. Using electron cryo-electron microscopy, we determined 61 Synechocystis PspA structures and observed in molecular detail how the structural plasticity of PspA rods is mediated by conformational changes at three hinge regions in the monomer and by the fixed and changing molecular contacts between protomers. Moreover, we reduced and increased the structural plasticity of PspA rods by removing the loop connecting helices α3/α4 and the addition of nucleotides, respectively. Based on our analysis of PspA-mediated membrane remodeling, we suggest that the observed mode of structural plasticity is a prerequisite for the biological function of ESCRT-III members.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"5 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992021","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

A PRE loop at the dac locus acts as a topological chromatin structure that restricts and specifies enhancer–promoter communication dac 基因座上的 PRE 环是一种拓扑染色质结构，它限制并指定了增强子与启动子之间的交流

Nature structural & molecular biology Pub Date : 2024-08-16 DOI: 10.1038/s41594-024-01375-7

Sandrine Denaud, Marion Bardou, Giorgio-Lucio Papadopoulos, Stefan Grob, Marco Di Stefano, Gonzalo Sabarís, Marcelo Nollmann, Bernd Schuettengruber, Giacomo Cavalli

{"title":"A PRE loop at the dac locus acts as a topological chromatin structure that restricts and specifies enhancer–promoter communication","authors":"Sandrine Denaud, Marion Bardou, Giorgio-Lucio Papadopoulos, Stefan Grob, Marco Di Stefano, Gonzalo Sabarís, Marcelo Nollmann, Bernd Schuettengruber, Giacomo Cavalli","doi":"10.1038/s41594-024-01375-7","DOIUrl":"https://doi.org/10.1038/s41594-024-01375-7","url":null,"abstract":"Three-dimensional (3D) genome folding has a fundamental role in the regulation of developmental genes by facilitating or constraining chromatin interactions between cis-regulatory elements (CREs). Polycomb response elements (PREs) are a specific kind of CRE involved in the memory of transcriptional states in Drosophila melanogaster. PREs act as nucleation sites for Polycomb group (PcG) proteins, which deposit the repressive histone mark H3K27me3, leading to the formation of a class of topologically associating domain (TAD) called a Polycomb domain. PREs can establish looping contacts that stabilize the gene repression of key developmental genes during development. However, the mechanism by which PRE loops fine-tune gene expression is unknown. Using clustered regularly interspaced short palindromic repeats and Cas9 genome engineering, we specifically perturbed PRE contacts or enhancer function and used complementary approaches including 4C-seq, Hi-C and Hi-M to analyze how chromatin architecture perturbation affects gene expression. Our results suggest that the PRE loop at the dac gene locus acts as a constitutive 3D chromatin scaffold during Drosophila development that forms independently of gene expression states and has a versatile function; it restricts enhancer–promoter communication and contributes to enhancer specificity.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992006","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

Topoisomerase-modulated genome-wide DNA supercoiling domains colocalize with nuclear compartments and regulate human gene expression 拓扑异构酶调控的全基因组DNA超卷曲结构域与核分区共定位并调控人类基因表达

Nature structural & molecular biology Pub Date : 2024-08-16 DOI: 10.1038/s41594-024-01377-5

Qian Yao, Linying Zhu, Zhen Shi, Subhadra Banerjee, Chongyi Chen

{"title":"Topoisomerase-modulated genome-wide DNA supercoiling domains colocalize with nuclear compartments and regulate human gene expression","authors":"Qian Yao, Linying Zhu, Zhen Shi, Subhadra Banerjee, Chongyi Chen","doi":"10.1038/s41594-024-01377-5","DOIUrl":"https://doi.org/10.1038/s41594-024-01377-5","url":null,"abstract":"DNA supercoiling is a biophysical feature of the double helix with a pivotal role in biological processes. However, understanding of DNA supercoiling in the chromatin remains limited. Here, we developed azide-trimethylpsoralen sequencing (ATMP-seq), a DNA supercoiling assay offering quantitative accuracy while minimizing genomic bias and background noise. Using ATMP-seq, we directly visualized transcription-dependent negative and positive twin-supercoiled domains around genes and mapped kilobase-resolution DNA supercoiling throughout the human genome. Remarkably, we discovered megabase-scale supercoiling domains (SDs) across all chromosomes that are modulated mainly by topoisomerases I and IIβ. Transcription activities, but not the consequent supercoiling accumulation in the local region, contribute to SD formation, indicating the long-range propagation of transcription-generated supercoiling. Genome-wide SDs colocalize with A/B compartments in both human and Drosophila cells but are distinct from topologically associating domains (TADs), with negative supercoiling accumulation at TAD boundaries. Furthermore, genome-wide DNA supercoiling varies between cell states and types and regulates human gene expression, underscoring the importance of supercoiling dynamics in chromatin regulation and function.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141992015","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

Structural basis of LRPPRC–SLIRP-dependent translation by the mitoribosome 米托里伯体依赖 LRPPRC-SLIRP 翻译的结构基础

Nature structural & molecular biology Pub Date : 2024-08-12 DOI: 10.1038/s41594-024-01365-9

Vivek Singh, J. Conor Moran, Yuzuru Itoh, Iliana C. Soto, Flavia Fontanesi, Mary Couvillion, Martijn A. Huynen, L. Stirling Churchman, Antoni Barrientos, Alexey Amunts

{"title":"Structural basis of LRPPRC–SLIRP-dependent translation by the mitoribosome","authors":"Vivek Singh, J. Conor Moran, Yuzuru Itoh, Iliana C. Soto, Flavia Fontanesi, Mary Couvillion, Martijn A. Huynen, L. Stirling Churchman, Antoni Barrientos, Alexey Amunts","doi":"10.1038/s41594-024-01365-9","DOIUrl":"https://doi.org/10.1038/s41594-024-01365-9","url":null,"abstract":"In mammalian mitochondria, mRNAs are cotranscriptionally stabilized by the protein factor LRPPRC (leucine-rich pentatricopeptide repeat-containing protein). Here, we characterize LRPPRC as an mRNA delivery factor and report its cryo-electron microscopy structure in complex with SLIRP (SRA stem-loop-interacting RNA-binding protein), mRNA and the mitoribosome. The structure shows that LRPPRC associates with the mitoribosomal proteins mS39 and the N terminus of mS31 through recognition of the LRPPRC helical repeats. Together, the proteins form a corridor for handoff of the mRNA. The mRNA is directly bound to SLIRP, which also has a stabilizing function for LRPPRC. To delineate the effect of LRPPRC on individual mitochondrial transcripts, we used RNA sequencing, metabolic labeling and mitoribosome profiling, which showed a transcript-specific influence on mRNA translation efficiency, with cyclooxygenase 1 and 2 translation being the most affected. Our data suggest that LRPPRC–SLIRP acts in recruitment of mitochondrial mRNAs to modulate their translation. Collectively, the data define LRPPRC–SLIRP as a regulator of the mitochondrial gene expression system.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"26 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918825","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

Structural basis of RfaH-mediated transcription–translation coupling RfaH 介导的转录-翻译耦合的结构基础

Nature structural & molecular biology Pub Date : 2024-08-08 DOI: 10.1038/s41594-024-01372-w

Vadim Molodtsov, Chengyuan Wang, Jing Zhang, Jason T. Kaelber, Gregor Blaha, Richard H. Ebright

{"title":"Structural basis of RfaH-mediated transcription–translation coupling","authors":"Vadim Molodtsov, Chengyuan Wang, Jing Zhang, Jason T. Kaelber, Gregor Blaha, Richard H. Ebright","doi":"10.1038/s41594-024-01372-w","DOIUrl":"https://doi.org/10.1038/s41594-024-01372-w","url":null,"abstract":"The NusG paralog RfaH mediates bacterial transcription–translation coupling in genes that contain a DNA sequence element, termed an ops site, required for pausing RNA polymerase (RNAP) and for loading RfaH onto the paused RNAP. Here, we report cryo-electron microscopy structures of transcription–translation complexes (TTCs) containing Escherichia coli RfaH. The results show that RfaH bridges RNAP and the ribosome, with the RfaH N-terminal domain interacting with RNAP and the RfaH C-terminal domain interacting with the ribosome. The results show that the distribution of translational and orientational positions of RNAP relative to the ribosome in RfaH-coupled TTCs is more restricted than in NusG-coupled TTCs because of the more restricted flexibility of the RfaH interdomain linker. The results further suggest that the structural organization of RfaH-coupled TTCs in the ‘loading state’, in which RNAP and RfaH are located at the ops site during formation of the TTC, is the same as the structural organization of RfaH-coupled TTCs in the ‘loaded state’, in which RNAP and RfaH are located at positions downstream of the ops site during function of the TTC. The results define the structural organization of RfaH-containing TTCs and set the stage for analysis of functions of RfaH during translation initiation and transcription–translation coupling.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"56 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141904613","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

Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε 人类前导链 DNA 聚合酶 Pol ε 进行子链合成和校对的结构基础

Nature structural & molecular biology Pub Date : 2024-08-07 DOI: 10.1038/s41594-024-01370-y

Johann J. Roske, Joseph T. P. Yeeles

引用次数: 0

The cyanobacterial protein VIPP1 forms ESCRT-III-like structures on lipid bilayers 蓝藻蛋白 VIPP1 在脂质双分子层上形成类似 ESCRT-III 的结构

Nature structural & molecular biology Pub Date : 2024-07-26 DOI: 10.1038/s41594-024-01367-7

Sichen Pan, Karin Gries, Benjamin D. Engel, Michael Schroda, Christoph A. Haselwandter, Simon Scheuring

{"title":"The cyanobacterial protein VIPP1 forms ESCRT-III-like structures on lipid bilayers","authors":"Sichen Pan, Karin Gries, Benjamin D. Engel, Michael Schroda, Christoph A. Haselwandter, Simon Scheuring","doi":"10.1038/s41594-024-01367-7","DOIUrl":"https://doi.org/10.1038/s41594-024-01367-7","url":null,"abstract":"The biogenesis and maintenance of thylakoid membranes require vesicle-inducing protein in plastids 1 (VIPP1). VIPP1 is a member of the endosomal sorting complex required for transport-III (ESCRT-III) superfamily, whose members form diverse filament-based supramolecular structures that facilitate membrane deformation and fission. VIPP1 cryo-electron microscopy (EM) structures in solution revealed helical rods and baskets of stacked rings, with amphipathic membrane-binding domains in the lumen. However, how VIPP1 interacts with membranes remains largely unknown. Here, using high-speed atomic force microscopy (HS-AFM), we show that VIPP1 assembles into right-handed chiral spirals and regular polygons on supported lipid bilayers via ESCRT-III-like filament assembly and dynamics. VIPP1 filaments grow clockwise into spirals through polymerization at a ring-shaped central polymerization hub, and into polygons through clockwise polymerization at the sector peripheries. Interestingly, VIPP1 initially forms Archimedean spirals, which upon maturation transform into logarithmic spirals through lateral annealing of strands to the outermore low-curvature spiral turns.","PeriodicalId":18822,"journal":{"name":"Nature structural & molecular biology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141764278","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

Genome dilution by cell growth drives starvation-like proteome remodeling in mammalian and yeast cells 细胞生长导致的基因组稀释推动了哺乳动物和酵母细胞中类似饥饿的蛋白质组重塑

Nature structural & molecular biology Pub Date : 2024-07-24 DOI: 10.1038/s41594-024-01353-z

Michael C. Lanz, Shuyuan Zhang, Matthew P. Swaffer, Inbal Ziv, Luisa Hernández Götz, Jacob Kim, Frank McCarthy, Daniel F. Jarosz, Joshua E. Elias, Jan M. Skotheim

引用次数: 0