Nature Structural & Molecular Biology最新文献_第4页

Closed and open structures of the eukaryotic magnesium channel Mrs2 reveal the auto-ligand-gating regulation mechanism 真核镁通道Mrs2的封闭和开放结构揭示了自配体门控调控机制。

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-28 DOI: 10.1038/s41594-024-01432-1

Ping Li, Shiyan Liu, Johan Wallerstein, Rhiza Lyne E. Villones, Peng Huang, Karin Lindkvist-Petersson, Gabriele Meloni, Kefeng Lu, Kristine Steen Jensen, Sara I. Liin, Pontus Gourdon

{"title":"Closed and open structures of the eukaryotic magnesium channel Mrs2 reveal the auto-ligand-gating regulation mechanism","authors":"Ping Li, Shiyan Liu, Johan Wallerstein, Rhiza Lyne E. Villones, Peng Huang, Karin Lindkvist-Petersson, Gabriele Meloni, Kefeng Lu, Kristine Steen Jensen, Sara I. Liin, Pontus Gourdon","doi":"10.1038/s41594-024-01432-1","DOIUrl":"10.1038/s41594-024-01432-1","url":null,"abstract":"The CorA/Mrs2 family of pentameric proteins are cardinal for the influx of Mg2+ across cellular membranes, importing the cation to mitochondria in eukaryotes. Yet, the conducting and regulation mechanisms of permeation remain elusive, particularly for the eukaryotic Mrs2 members. Here, we report closed and open Mrs2 cryo-electron microscopy structures, accompanied by functional characterization. Mg2+ flux is permitted by a narrow pore, gated by methionine and arginine residues in the closed state. Transition between the conformations is orchestrated by two pairs of conserved sensor-serving Mg2+-binding sites in the mitochondrial matrix lumen, located in between monomers. At lower levels of Mg2+, these ions are stripped, permitting an alternative, symmetrical shape, maintained by the RDLR motif that replaces one of the sensor site pairs in the open conformation. Thus, our findings collectively establish the molecular basis for selective Mg2+ influx of Mrs2 and an auto-ligand-gating regulation mechanism. Here, the authors demonstrate how Mrs2, critical for import of Mg2+ into the mitochondria, transitions from open and closed five-fold symmetric states to control the influx of Mg2+ using an auto-ligand-gating regulation mechanism.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 3","pages":"491-501"},"PeriodicalIF":12.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01432-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751154","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}

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Looking back at the timely launch of Nature Structural Biology in 1994 回顾1994年《自然-结构生物学》及时创刊。

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-28 DOI: 10.1038/s41594-024-01436-x

Christian Cambillau

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Structure and function of the human mitochondrial MRS2 channel 人线粒体MRS2通道的结构和功能。

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-28 DOI: 10.1038/s41594-024-01420-5

Zhihui He, Yung-Chi Tu, Chen-Wei Tsai, Jonathan Mount, Jingying Zhang, Ming-Feng Tsai, Peng Yuan

{"title":"Structure and function of the human mitochondrial MRS2 channel","authors":"Zhihui He, Yung-Chi Tu, Chen-Wei Tsai, Jonathan Mount, Jingying Zhang, Ming-Feng Tsai, Peng Yuan","doi":"10.1038/s41594-024-01420-5","DOIUrl":"10.1038/s41594-024-01420-5","url":null,"abstract":"The human mitochondrial RNA splicing 2 protein (MRS2) has been implicated in Mg2+ transport across mitochondrial inner membranes, thus having an important role in Mg2+ homeostasis critical for mitochondrial integrity and function. However, the molecular mechanisms underlying its fundamental channel properties such as ion selectivity and regulation remain unclear. Here we present a structural and functional investigation of MRS2. Cryo-electron microscopy structures in various ionic conditions reveal a pentameric channel architecture and the molecular basis of ion permeation and potential regulation mechanisms. Electrophysiological analyses demonstrate that MRS2 is a Ca2+-regulated, nonselective channel permeable to Mg2+, Ca2+, Na+ and K+, which contrasts with its prokaryotic ortholog, CorA, operating as a Mg2+-gated Mg2+ channel. Moreover, a conserved arginine ring within the pore of MRS2 functions to restrict cation movements, thus preventing the channel from collapsing the proton motive force that drives mitochondrial adenosine triphosphate synthesis. Together, our results provide a molecular framework for further understanding MRS2 in mitochondrial function and disease. Using structural and electrophysiological analysis, authors demonstrated that the mitochondrial MRS2 channel is a calcium-regulated nonselective cation channel.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 3","pages":"459-468"},"PeriodicalIF":12.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751090","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}

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Keeping in touch with the road not taken 与未走的路保持联系。

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-28 DOI: 10.1038/s41594-024-01443-y

Javier Apfeld

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Diverse anti-NMDAR autoantibodies from individuals with encephalitis 来自脑炎患者的多种抗NMDAR自身抗体

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-27 DOI: 10.1038/s41594-024-01435-y

Zoe Jamet, Frederic Villega, Laurent Groc

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A lesson in symmetry 一堂对称课

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-27 DOI: 10.1038/s41594-024-01437-w

Magdalena Boncler

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Evolution and function of chromatin domains across the tree of life 生命树上染色质结构域的进化与功能

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-26 DOI: 10.1038/s41594-024-01427-y

Michael-Florian Szalay, Blanka Majchrzycka, Ivana Jerković, Giacomo Cavalli, Daniel M. Ibrahim

{"title":"Evolution and function of chromatin domains across the tree of life","authors":"Michael-Florian Szalay, Blanka Majchrzycka, Ivana Jerković, Giacomo Cavalli, Daniel M. Ibrahim","doi":"10.1038/s41594-024-01427-y","DOIUrl":"10.1038/s41594-024-01427-y","url":null,"abstract":"The genome of all organisms is spatially organized to function efficiently. The advent of genome-wide chromatin conformation capture (Hi-C) methods has revolutionized our ability to probe the three-dimensional (3D) organization of genomes across diverse species. In this Review, we compare 3D chromatin folding from bacteria and archaea to that in mammals and plants, focusing on topology at the level of gene regulatory domains. In doing so, we consider systematic similarities and differences that hint at the origin and evolution of spatial chromatin folding and its relation to gene activity. We discuss the universality of spatial chromatin domains in all kingdoms, each encompassing one to several genes. We also highlight differences between organisms and suggest that similar features in Hi-C matrices do not necessarily reflect the same biological process or function. Furthermore, we discuss the evolution of domain boundaries and boundary-forming proteins, which indicates that structural maintenance of chromosome (SMC) proteins and the transcription machinery are the ancestral sculptors of the genome. Architectural proteins such as CTCF serve as clade-specific determinants of genome organization. Finally, studies in many non-model organisms show that, despite the ancient origin of 3D chromatin folding and its intricate link to gene activity, evolution tolerates substantial changes in genome organization. Szalay et al. discuss cross-kingdom similarities and differences in 3D chromatin folding in relation to gene regulation, including in bacteria, archaea, mammals and plants. This comparison reveals certain factors as ancestral sculptors of the genome, but also that evolution tolerates considerable variety in genome organization.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"31 12","pages":"1824-1837"},"PeriodicalIF":12.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142712799","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}

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The yeast genome is globally accessible in living cells 酵母基因组可在活细胞中全球访问

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-25 DOI: 10.1038/s41594-024-01318-2

Hemant K. Prajapati, Peter R. Eriksson, Paul A. Elizalde, Christopher T. Coey, Zhuwei Xu, David J. Clark

{"title":"The yeast genome is globally accessible in living cells","authors":"Hemant K. Prajapati, Peter R. Eriksson, Paul A. Elizalde, Christopher T. Coey, Zhuwei Xu, David J. Clark","doi":"10.1038/s41594-024-01318-2","DOIUrl":"10.1038/s41594-024-01318-2","url":null,"abstract":"Eukaryotic genomes are packaged into chromatin, which is composed of condensed filaments of regularly spaced nucleosomes, resembling beads on a string. The nucleosome contains ~147 bp of DNA wrapped almost twice around a central core histone octamer. The packaging of DNA into chromatin represents a challenge to transcription factors and other proteins requiring access to their binding sites. Consequently, control of DNA accessibility is thought to play a key role in gene regulation. Here we measure DNA accessibility genome wide in living budding yeast cells by inducible expression of DNA methyltransferases. We find that the genome is globally accessible in living cells, unlike in isolated nuclei, where DNA accessibility is severely restricted. Gene bodies are methylated at only slightly slower rates than promoters, indicating that yeast chromatin is highly dynamic in vivo. In contrast, silenced loci and centromeres are strongly protected. Global shifts in nucleosome positions occur in cells as they are depleted of ATP-dependent chromatin remodelers, suggesting that nucleosome dynamics result from competition among these enzymes. We conclude that chromatin is in a state of continuous flux in living cells, but static in nuclei, suggesting that DNA packaging in yeast is not generally repressive. The authors measure the accessibility of the yeast genome using DNA methylases. They show that the genome is globally accessible in living cells, except for centromeres and silenced loci, unlike in isolated nuclei, in which accessibility is strictly limited.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 2","pages":"247-256"},"PeriodicalIF":12.5,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41594-024-01318-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697074","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}

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Structural insights into SV2A and the mechanism of racetam anticonvulsants 对 SV2A 的结构洞察以及拉西坦类抗惊厥药的作用机制

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-22 DOI: 10.1038/s41594-024-01430-3

Mazdak M. Bradberry, Edwin R. Chapman

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Na+-V-ATPase inhibitor curbs VRE growth and unveils Na+ pathway structure Na+-V-ATP酶抑制剂抑制VRE生长并揭示Na+通路结构

IF 12.5 1区生物学

Nature Structural & Molecular Biology Pub Date : 2024-11-21 DOI: 10.1038/s41594-024-01419-y

Kano Suzuki, Yoshiyuki Goto, Akihiro Otomo, Kouki Shimizu, Shohei Abe, Katsuhiko Moriyama, Satoshi Yasuda, Yusuke Hashimoto, Jun Kurushima, Sho Mikuriya, Fabiana L. Imai, Naruhiko Adachi, Masato Kawasaki, Yumi Sato, Satoshi Ogasawara, So Iwata, Toshiya Senda, Mitsunori Ikeguchi, Haruyoshi Tomita, Ryota Iino, Toshio Moriya, Takeshi Murata

{"title":"Na+-V-ATPase inhibitor curbs VRE growth and unveils Na+ pathway structure","authors":"Kano Suzuki, Yoshiyuki Goto, Akihiro Otomo, Kouki Shimizu, Shohei Abe, Katsuhiko Moriyama, Satoshi Yasuda, Yusuke Hashimoto, Jun Kurushima, Sho Mikuriya, Fabiana L. Imai, Naruhiko Adachi, Masato Kawasaki, Yumi Sato, Satoshi Ogasawara, So Iwata, Toshiya Senda, Mitsunori Ikeguchi, Haruyoshi Tomita, Ryota Iino, Toshio Moriya, Takeshi Murata","doi":"10.1038/s41594-024-01419-y","DOIUrl":"10.1038/s41594-024-01419-y","url":null,"abstract":"Vancomycin-resistant Enterococcus faecium (VRE) is a major cause of nosocomial infections, particularly endocarditis and sepsis. With the diminishing effectiveness of antibiotics against VRE, new antimicrobial agents are urgently needed. Our previous research demonstrated the crucial role of Na+-transporting V-ATPase in Enterococcus hirae for growth under alkaline conditions. In this study, we identified a compound, V-161, from 70,600 compounds, which markedly inhibits E. hirae V-ATPase activity. V-161 not only inhibits VRE growth in alkaline conditions but also significantly suppresses VRE colonization in the mouse small intestine. Furthermore, we unveiled the high-resolution structure of the membrane VO part due to V-161 binding. V-161 binds to the interface of the c-ring and a-subunit, constituting the Na+ transport pathway in the membrane, thereby halting its rotation. This structural insight presents potential avenues for developing therapeutic agents for VRE treatment and elucidates the Na+ transport pathway and mechanism. The authors identify V-161, a compound that inhibits enterococcal Na+-V-ATPase and reduces VRE colonization in mice. The high-resolution structure of V-161 reveals its action on the Na+ transport pathway, offering new therapeutic insights.","PeriodicalId":49141,"journal":{"name":"Nature Structural & Molecular Biology","volume":"32 3","pages":"450-458"},"PeriodicalIF":12.5,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684225","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}

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