Nature Structural & Molecular Biology最新文献

{"title":"Bacterial clippases shift ubiquitin","authors":"Irene Serrano","doi":"10.1038/s41594-025-01545-1","DOIUrl":"10.1038/s41594-025-01545-1","url":null,"abstract":"","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 4","pages":"587-587"},"PeriodicalIF":10.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814053","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}

{"title":"Timing of complex I activity and lifespan control","authors":"Melina Casadio","doi":"10.1038/s41594-025-01541-5","DOIUrl":"10.1038/s41594-025-01541-5","url":null,"abstract":"","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 4","pages":"587-587"},"PeriodicalIF":10.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814054","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}

{"title":"Accessible technology for diploid high-order 3D human genome analysis","authors":"","doi":"10.1038/s41594-025-01519-3","DOIUrl":"10.1038/s41594-025-01519-3","url":null,"abstract":"We developed a method that improves the detection of haplotype-assigned chromatin interactions in humans by over tenfold, using far less data than traditional methods. This advance enabled an almost complete diploid 3D genome map, making high-order phased chromatin interaction studies more accessible to researchers.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 7","pages":"1141-1142"},"PeriodicalIF":10.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143814055","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}

{"title":"Ion-conducting and gating molecular mechanisms of channelrhodopsin revealed by true-atomic-resolution structures of open and closed states","authors":"Dmitrii Zabelskii, Sergey Bukhdruker, Siarhei Bukhalovich, Fedor Tsybrov, Gerrit H. U. Lamm, Roman Astashkin, Demid Doroginin, Grigory Matveev, Vsevolod Sudarev, Alexander Kuzmin, Egor Zinovev, Anastasiia Vlasova, Yury Ryzhykau, Nikolay Ilyinsky, Ivan Gushchin, Gleb Bourenkov, Alexey Alekseev, Adam Round, Josef Wachtveitl, Ernst Bamberg, Valentin Gordeliy","doi":"10.1038/s41594-025-01488-7","DOIUrl":"10.1038/s41594-025-01488-7","url":null,"abstract":"Channelrhodopsins (ChRs) have emerged as major optogenetics tools, particularly in neuroscience. Despite their importance, the molecular mechanism of ChR opening remains elusive. Moreover, all reported structures of ChRs correspond to either a closed or an early intermediate state and lack the necessary level of detail owing to the limited resolution. Here we present the structures of the closed and open states of a cation-conducting ChR, OLPVR1, from Organic Lake phycodnavirus, belonging to the family of viral ChRs solved at 1.1- and 1.3-Å resolution at physiologically relevant pH conditions (pH 8.0). OLPVR1 was expressed in Escherichia coli and crystallized using an in meso approach, and the structures were solved by X-ray crystallography. We also present the structure of the OLPVR1 protonated state at acidic pH (pH 2.5) at 1.4-Å resolution. Together, these three structures elucidate the molecular mechanisms of the channel’s opening and permeability in detail. Extensive functional studies support the proposed mechanisms. Channel opening is controlled by isomerization of the retinal cofactor, triggering protonation of proton acceptors and deprotonation of proton donors located in the three gates of the channel. The E51 residue in the core of the central gate (similar to E90 of ChR2 from Chlamydomonas reinhardtii) plays a key role in the opening of the channel. E51 flips out of the gate and towards the proton acceptor D200 (D253 in ChR2 in C. reinhardtii), establishing a hydrogen bond between them. Despite differences in subfamilies of ChRs, they share a common gate–cavity architecture, suggesting that they could have similar general gating mechanisms. These results enabled us to design viral rhodopsin with improved properties for optogenetic applications. The structural data and mechanisms might also be helpful for better understanding other ChRs and their engineering. Channelrhodopsins (ChRs) are primary tools for precise optical control over living cells. Structures of a viral ChR, OLPVR1, in closed (1.1 Å) and open (1.3 Å) states reveal the key details of its molecular mechanism.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 8","pages":"1347-1357"},"PeriodicalIF":10.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805681","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}

{"title":"Shigella flexneri evades LPS ubiquitylation through IpaH1.4-mediated degradation of RNF213","authors":"Katerina Naydenova, Keith B. Boyle, Claudio Pathe, Prathyush Pothukuchi, Ana Crespillo-Casado, Felix Scharte, Pierre-Mehdi Hammoudi, Elsje G. Otten, Neal M. Alto, Felix Randow","doi":"10.1038/s41594-025-01530-8","DOIUrl":"10.1038/s41594-025-01530-8","url":null,"abstract":"Pathogens have evolved diverse strategies to counteract host immunity. Ubiquitylation of lipopolysaccharide (LPS) on cytosol-invading bacteria by the E3 ligase RNF213 creates ‘eat me’ signals for antibacterial autophagy, but whether and how cytosol-adapted bacteria avoid LPS ubiquitylation remains poorly understood. Here, we show that the enterobacterium Shigella flexneri actively antagonizes LPS ubiquitylation through IpaH1.4, a secreted effector protein with ubiquitin E3 ligase activity. IpaH1.4 binds to RNF213, ubiquitylates it and targets it for proteasomal degradation, thus counteracting host-protective LPS ubiquitylation. To understand how IpaH1.4 recognizes RNF213, we determined the cryogenic electron microscopy structure of the IpaH1.4–RNF213 complex. The specificity of the interaction is achieved through the leucine-rich repeat of IpaH1.4, which binds the RING domain of RNF213 by hijacking the conserved RING interface required for binding to ubiquitin-charged E2 enzymes. IpaH1.4 also targets other E3 ligases involved in inflammation and immunity through binding to the E2-interacting face of their RING domains, including the E3 ligase LUBAC that is required for the synthesis of M1-linked ubiquitin chains on cytosol-invading bacteria downstream of RNF213. We conclude that IpaH1.4 has evolved to antagonize multiple antibacterial and proinflammatory host E3 ligases. Naydenova, Boyle and Pathe et al. report that Shigella uses the ubiquitin E3 ligase IpaH1.4 to evade lipopolysaccharide ubiquitylation in infected cells by degrading the host E3 ligase RNF213. Using cryo-electron microscopy, they present the structural basis of this interaction and the mechanism of immune evasion.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 9","pages":"1741-1751"},"PeriodicalIF":10.1,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01530-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805682","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}

{"title":"Finding and recycling stalled spliceosomes","authors":"Charles C. Query, Jadwiga Meissner, Maria M. Konarska","doi":"10.1038/s41594-025-01536-2","DOIUrl":"10.1038/s41594-025-01536-2","url":null,"abstract":"Splicing of pre-mRNA requires both high fidelity and enormous sequence flexibility, inevitably resulting in aberrant, stalled complexes that must be discarded. A study now describes cryo-EM structures of stalled complexes poised for disassembly, determining aspects of aberrant complex recognition and splicing quality control.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 5","pages":"775-776"},"PeriodicalIF":10.1,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797801","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}

{"title":"Heritable maintenance of chromatin modifications confers transcriptional memory of interferon-γ signaling","authors":"Pawel Mikulski, Sahar S. H. Tehrani, Anna Kogan, Izma Abdul-Zani, Emer Shell, Louise James, Brent J. Ryan, Lars E. T. Jansen","doi":"10.1038/s41594-025-01522-8","DOIUrl":"10.1038/s41594-025-01522-8","url":null,"abstract":"Interferon-γ (IFNγ) transiently activates genes related to inflammation and innate immunity. A subset of targets retain a mitotically heritable memory of prior IFNγ exposure, resulting in hyperactivation upon re-exposure through poorly understood mechanisms. Here, we discover that the transcriptionally permissive chromatin marks H3K4me1, H3K14ac and H4K16ac are established during IFNγ priming and are selectively maintained on a cluster of guanylate-binding protein (GBP) genes in dividing human cells in the absence of transcription. The histone acetyltransferase KAT7 is required for H3K14ac deposition at GBP genes and for accelerated GBP reactivation upon re-exposure to IFNγ. In naive cells, the GBP cluster is maintained in a low-level repressive chromatin state, marked by H3K27me3, limiting priming through a PRC2-dependent mechanism. Unexpectedly, IFNγ priming results in transient accumulation of this repressive mark despite active gene expression. However, during the memory phase, H3K27 methylation is selectively depleted from primed GBP genes, facilitating hyperactivation. Furthermore, we identified a cis-regulatory element that forms transient, long-range contacts across the GBP cluster and acts as a repressor, curbing hyperactivation of previously IFNγ-primed cells. Our results provide insight into the chromatin basis for the long-term transcriptional memory of IFNγ signaling, which might contribute to enhanced innate immunity. Mikulski et al. identify a distinct chromatin structure at clustered GBP innate immune genes that preserves a mitotically heritable memory of prior priming by interferon-γ.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 7","pages":"1255-1267"},"PeriodicalIF":10.1,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01522-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143775688","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}

{"title":"O-GlcNAc transferase is a key regulator of DNA methylation and transposon silencing","authors":"","doi":"10.1038/s41594-025-01507-7","DOIUrl":"10.1038/s41594-025-01507-7","url":null,"abstract":"Disruption of the enzyme O-GlcNAc transferase in mouse embryonic stem cells unleashes the activity of TET enzymes, which cause genome-wide decreases in DNA methylation and increases in DNA hydroxymethylation. This leads to de-repression of transposable elements, as well as the activation of some nearby genes.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 7","pages":"1137-1138"},"PeriodicalIF":10.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758693","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}

{"title":"Author Correction: DELE1 oligomerization promotes integrated stress response activation","authors":"Jie Yang, Kelsey R. Baron, Daniel E. Pride, Anette Schneemann, Xiaoyan Guo, Wenqian Chen, Albert S. Song, Giovanni Aviles, Martin Kampmann, R. Luke Wiseman, Gabriel C. Lander","doi":"10.1038/s41594-025-01547-z","DOIUrl":"10.1038/s41594-025-01547-z","url":null,"abstract":"","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 4","pages":"768-768"},"PeriodicalIF":10.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41594-025-01547-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772776","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}

{"title":"Structural basis for membrane remodeling by the AP5–SPG11–SPG15 complex","authors":"Xinyi Mai, Yang Wang, Xi Wang, Ming Liu, Fei Teng, Zheng Liu, Ming-Yuan Su, Goran Stjepanovic","doi":"10.1038/s41594-025-01500-0","DOIUrl":"10.1038/s41594-025-01500-0","url":null,"abstract":"The human spastizin (spastic paraplegia 15, SPG15) and spatacsin (spastic paraplegia 11, SPG11) complex is involved in the formation of lysosomes, and mutations in these two proteins are linked with hereditary autosomal-recessive spastic paraplegia. SPG11–SPG15 can cooperate with the fifth adaptor protein complex (AP5) involved in membrane sorting of late endosomes. We employed cryogenic-electron microscopy and in silico predictions to investigate the structural assemblies of the SPG11–SPG15 and AP5–SPG11–SPG15 complexes. The W-shaped SPG11–SPG15 intertwined in a head-to-head fashion, and the N-terminal region of SPG11 is required for AP5 complex interaction and assembly. The AP5 complex is in a super-open conformation. Our findings reveal that the AP5–SPG11–SPG15 complex can bind PI3P molecules, sense membrane curvature and drive membrane remodeling in vitro. These studies provide insights into the structure and function of the spastic paraplegia AP5–SPG11–SPG15 complex, which is essential for the initiation of autolysosome tubulation. Mai and colleagues present cryo-electron microscopy structures of the SPG11–SPG15 and AP5–SPG11–SPG15 complex, offering insights into mechanisms of autophagic lysosome reformation and retrograde trafficking.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 8","pages":"1334-1346"},"PeriodicalIF":10.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143758177","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}