综合性期刊最新文献

{"title":"Binding site maturation modulated by molecular density underlies Ndc80 binding to kinetochore receptor CENP-T","authors":"Ekaterina V. Tarasovetc, Gunter B. Sissoko, Aleksandr Maiorov, Anna S. Mukhina, Fazoil I. Ataullakhanov, Iain M. Cheeseman, Ekaterina L. Grishchuk","doi":"10.1073/pnas.2401344121","DOIUrl":"https://doi.org/10.1073/pnas.2401344121","url":null,"abstract":"Macromolecular assembly depends on tightly regulated pairwise binding interactions that are selectively favored at assembly sites while being disfavored in the soluble phase. This selective control can arise due to molecular density-enhanced binding, as recently found for the kinetochore scaffold protein CENP-T. When clustered, CENP-T recruits markedly more Ndc80 complexes than its monomeric counterpart, but the underlying molecular basis remains elusive. Here, we use quantitative in vitro assays to reveal two distinct mechanisms driving this behavior. First, Ndc80 binding to CENP-T is a two-step process: initially, Ndc80 molecules rapidly associate and dissociate from disordered N-terminal binding sites on CENP-T. Over time, these sites undergo maturation, resulting in stronger Ndc80 retention. Second, we find that this maturation transition is regulated by a kinetic barrier that is sensitive to the molecular environment. In the soluble phase, binding site maturation is slow, but within CENP-T clusters, this process is markedly accelerated. Notably, the two Ndc80 binding sites in human CENP-T exhibit distinct maturation rates and environmental sensitivities, which correlate with their different amino acid content and predicted binding conformations. This clustering-induced maturation is evident in dividing human cells, suggesting a distinct regulatory entry point for controlling kinetochore assembly. We propose that the tunable acceleration of binding site maturation by molecular crowding may represent a general mechanism for promoting the formation of macromolecular structures.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"31 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chiral π domain walls composed of twin half-integer surface disclinations in ferroelectric nematic liquid crystals","authors":"Shengzhu Yi, Zening Hong, Zhongjie Ma, Chao Zhou, Miao Jiang, Xiang Huang, Mingjun Huang, Satoshi Aya, Rui Zhang, Qi-Huo Wei","doi":"10.1073/pnas.2413879121","DOIUrl":"https://doi.org/10.1073/pnas.2413879121","url":null,"abstract":"Ferroelectric nematic liquid crystals are polar fluids characterized by microscopic orientational ordering and macroscopic spontaneous polarizations. Within these fluids, domain walls that separate regions of different polarizations are ubiquitous. We demonstrate that the π walls in films of the polar fluids consist of twin half-integer surface disclinations spaced horizontally, enclosing a subdomain where the polarization exhibits left- or right-handed π twists across the film. The degenerate geometric arrangements of the twin disclinations generate kinks and antikinks, parting subdomains of opposite chirality, like the spin-up and spin-down in Ising chains. The hierarchical structures dictate that field-driven polar switching undergo two-step annihilations of the surface disclinations. These findings provide an insight for both comprehending other walls in the polar fluids and domain engineering crucial for advancing their nonlinear and optoelectronic applications.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"13 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Kisspeptin-10 binding to Gpr54 in osteoclasts prevents bone loss by activating Dusp18-mediated dephosphorylation of Src","authors":"Zhenxi Li, Xinghai Yang, Ruifeng Fu, Zhipeng Wu, Shengzhao Xu, Jian Jiao, Ming Qian, Long Zhang, Chunbiao Wu, Tianying Xie, Jiqiang Yao, Zhixiang Wu, Wenjun Li, Guoli Ma, Yu You, Yihua Chen, Han-kun Zhang, Yiyun Cheng, Xiaolong Tang, Pengfei Wu, Gewei Lian, Haifeng Wei, Jian Zhao, Jianrong Xu, Lianzhong Ai, Stefan Siwko, Yue Wang, Jin Ding, Gaojie Song, Jian Luo, Mingyao Liu, Jianru Xiao","doi":"10.1038/s41467-024-55352-1","DOIUrl":"https://doi.org/10.1038/s41467-024-55352-1","url":null,"abstract":"<p>Correction to: <i>Nature Communications</i> https://doi.org/10.1038/s41467-024-44852-9, published online 12 February 2024</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"64 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Signatures of ambient pressure superconductivity in thin film La3Ni2O7","authors":"Eun Kyo Ko, Yijun Yu, Yidi Liu, Lopa Bhatt, Jiarui Li, Vivek Thampy, Cheng-Tai Kuo, Bai Yang Wang, Yonghun Lee, Kyuho Lee, Jun-Sik Lee, Berit H. Goodge, David A. Muller, Harold Y. Hwang","doi":"10.1038/s41586-024-08525-3","DOIUrl":"https://doi.org/10.1038/s41586-024-08525-3","url":null,"abstract":"<p>Recently, the bilayer nickelate La₃Ni₂O₇ has been discovered as a new superconductor with transition temperature <i>T</i>_c near 80 K under high pressure^1–3. Despite extensive theoretical and experimental work to understand the nature of its superconductivity^4–29, the requirement of extreme pressure restricts the use of many experimental probes and limits its application potential. Here, we present signatures of superconductivity in La₃Ni₂O₇ thin films at ambient pressure, facilitated by the application of epitaxial compressive strain. The onset <i>T</i>_c varies approximately from 26 K to 42 K, with higher <i>T</i>_c values correlating with smaller in-plane lattice constants. We observed the co-existence of other Ruddlesden-Popper phases within the films and dependence of transport behavior with ozone annealing, suggesting that the observed low zero resistance <i>T</i>_c of around 2 K can be attributed to stacking defects, grain boundaries, and oxygen stoichiometry. This finding initiates numerous opportunities to stabilize and study superconductivity in bilayer nickelates at ambient pressure, and to facilitate the broad understanding of the ever-growing number of high temperature and unconventional superconductors in the transition metal oxides.</p>","PeriodicalId":18787,"journal":{"name":"Nature","volume":"40 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing strong inducible synthetic promoters in yeasts","authors":"Masahiro Tominaga, Yoko Shima, Kenta Nozaki, Yoichiro Ito, Masataka Someda, Yuji Shoya, Noritaka Hashii, Chihiro Obata, Miho Matsumoto-Kitano, Kohei Suematsu, Tadashi Matsukawa, Keita Hosoya, Noriko Hashiba, Akihiko Kondo, Jun Ishii","doi":"10.1038/s41467-024-54865-z","DOIUrl":"https://doi.org/10.1038/s41467-024-54865-z","url":null,"abstract":"<p>Inducible promoters are essential for precise control of target gene expression in synthetic biological systems. However, engineering eukaryotic promoters is often more challenging than engineering prokaryotic promoters due to their greater mechanistic complexity. In this study, we describe a simple and reliable approach for constructing strongly inducible synthetic promoters with minimum leakiness in yeasts. The results indicate that the leakiness of yeast-inducible synthetic promoters is primarily the result of cryptic transcriptional activation of heterologous sequences that may be avoided by appropriate insulation and operator mutagenesis. Our promoter design approach has successfully generated robust, inducible promoters that achieve a &gt; 10³-fold induction in reporter gene expression. The utility of these promoters is demonstrated by using them to produce various biologics with titers up to 2 g/L, including antigens designed to raise specific antibodies against a SARS-CoV-2 omicron variant through chicken immunization.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"87 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"How to find your place in science through an industry postdoc","authors":"","doi":"10.1038/d41586-024-04169-5","DOIUrl":"https://doi.org/10.1038/d41586-024-04169-5","url":null,"abstract":"Three researchers talk about life in companies and the key to unlocking opportunities.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"10 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142849478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of proton release during water oxidation in Photosystem II","authors":"Friederike Allgöwer, Maximilian C. Pöverlein, A. William Rutherford, Ville R. I. Kaila","doi":"10.1073/pnas.2413396121","DOIUrl":"https://doi.org/10.1073/pnas.2413396121","url":null,"abstract":"Photosystem II (PSII) catalyzes light-driven water oxidation that releases dioxygen into our atmosphere and provides the electrons needed for the synthesis of biomass. The catalysis occurs in the oxygen-evolving oxo-manganese-calcium (Mn <jats:sub>4</jats:sub> O <jats:sub>5</jats:sub> Ca) cluster that drives the oxidation and deprotonation of substrate water molecules leading to the O <jats:sub>2</jats:sub> formation. However, despite recent advances, the mechanism of these reactions remains unclear and much debated. Here, we show that the light-driven Tyr161 <jats:sub>D1</jats:sub> (Y <jats:sub>z</jats:sub> ) oxidation adjacent to the Mn <jats:sub>4</jats:sub> O <jats:sub>5</jats:sub> Ca cluster, decreases the barrier for proton transfer from the putative substrate water molecule (W3/W <jats:sub>x</jats:sub> ) to Glu310 <jats:sub>D2</jats:sub> , accessible to the luminal bulk. By combining hybrid quantum/classical (QM/MM) free energy calculations with atomistic molecular dynamics simulations, we probe the energetics of the proton transfer along the Cl1 pathway. We demonstrate that the proton transfer occurs via water molecules and a cluster of conserved carboxylates, driven by redox-triggered electric fields directed along the pathway. Glu65 <jats:sub>D1</jats:sub> establishes a local molecular gate that controls the proton transfer to the luminal bulk, while Glu312 <jats:sub>D2</jats:sub> acts as a local proton storage site. The identified gating region could be important in preventing backflow of protons to the Mn <jats:sub>4</jats:sub> O <jats:sub>5</jats:sub> Ca cluster. The structural changes, derived here based on the dark-state PSII structure, strongly support recent time-resolved X-ray free electron laser data of the S <jats:sub>3</jats:sub> → S <jats:sub>4</jats:sub> transition (Bhowmick <jats:italic>et al</jats:italic> . Nature 617 , 2023) and reveal the mechanistic basis underlying deprotonation of the substrate water molecules. Our findings provide insight into the water oxidation mechanism of PSII and show how the interplay between redox-triggered electric fields, ion-pairs, and hydration effects control proton transport reactions.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"70 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Confinement-sensitive volume regulation dynamics via high-speed nuclear morphological measurements","authors":"Yixuan Li, Hui Ting Ong, Hongyue Cui, Xu Gao, Jia Wen Nicole Lee, Yuqi Guo, Rong Li, Fabrizio A. Pennacchio, Paolo Maiuri, Artem K. Efremov, Andrew W. Holle","doi":"10.1073/pnas.2408595121","DOIUrl":"https://doi.org/10.1073/pnas.2408595121","url":null,"abstract":"Diverse tissues in vivo present varying degrees of confinement, constriction, and compression to migrating cells in both homeostasis and disease. The nucleus in particular is subjected to external forces by the physical environment during confined migration. While many systems have been developed to induce nuclear deformation and analyze resultant functional changes, much remains unclear about dynamic volume regulation in confinement due to limitations in time resolution and difficulty imaging in PDMS-based microfluidic chips. Standard volumetric measurement relies on confocal microscopy, which suffers from high phototoxicity, slow speed, limited throughput, and artifacts in fast-moving cells. To address this, we developed a form of double fluorescence exclusion microscopy, designed to function at the interface of microchannel-based PDMS sidewalls, that can track cellular and nuclear volume dynamics during confined migration. By verifying the vertical symmetry of nuclei in confinement, we obtained computational estimates of nuclear surface area. We then tracked nuclear volume and surface area under physiological confinement at a time resolution exceeding 30 frames per minute. We find that during self-induced entrance into confinement, the cell rapidly expands its surface area until a threshold is reached, followed by a rapid decrease in nuclear volume. We next used osmotic shock as a tool to alter nuclear volume in confinement, and found that the nuclear response to hypo-osmotic shock in confinement does not follow classical scaling laws, suggesting that the limited expansion potential of the nuclear envelope might be a constraining factor in nuclear volume regulation in confining environments in vivo.","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":"31 1","pages":""},"PeriodicalIF":11.1,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142858548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"dCasMINI-mediated therapy rescues photoreceptors degeneration in a mouse model of retinitis pigmentosa","authors":"Qing Wang, Xiaoshu Xu, Siyu Chen, Rui Lu, Liang Li, Chien-Hui Lo, Zhiquan Liu, Ke Ning, Tingting Li, Tia J. Kowal, Biao Wang, Mary E. Hartnett, Sui Wang, Lei S. Qi, Yang Sun","doi":"10.1126/sciadv.adn7540","DOIUrl":"https://doi.org/10.1126/sciadv.adn7540","url":null,"abstract":"Retinitis pigmentosa (RP) is characterized by degeneration of rod and cone photoreceptors that progresses to irreversible blindness. Now, there are no mutation-agnostic approaches to treat RP. Here, we utilized a single adeno-associated virus (AAV)–based CRISPR activation system to activate phosphodiesterase 6B (Pde6b) to mitigate the severe degeneration in <jats:italic>Pde6a</jats:italic> <jats:sup>nmf363</jats:sup> mice. We demonstrate that transcriptional activation of <jats:italic>Pde6b</jats:italic> can rescue the loss of <jats:italic>Pde6a</jats:italic> , with preservation of retinal structure, restoration of electroretinography responses, and improvement of visual function as assessed by optokinetic response and looming-induced escape behaviors. These findings demonstrate the therapeutic potential of a dCasMINI-mediated activation strategy that provides a mutation-independent treatment for retinal degeneration. This study offers a promising therapeutic approach for RP and potentially other forms of genetic diseases.","PeriodicalId":21609,"journal":{"name":"Science Advances","volume":"30 1","pages":""},"PeriodicalIF":13.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of pseudosymmetric protein hetero-oligomers","authors":"Ryan D. Kibler, Sangmin Lee, Madison A. Kennedy, Basile I. M. Wicky, Stella M. Lai, Marius M. Kostelic, Ann Carr, Xinting Li, Cameron M. Chow, Tina K. Nguyen, Lauren Carter, Vicki H. Wysocki, Barry L. Stoddard, David Baker","doi":"10.1038/s41467-024-54913-8","DOIUrl":"https://doi.org/10.1038/s41467-024-54913-8","url":null,"abstract":"<p>Pseudosymmetric hetero-oligomers with three or more unique subunits with overall structural (but not sequence) symmetry play key roles in biology, and systematic approaches for generating such proteins de novo would provide new routes to controlling cell signaling and designing complex protein materials. However, the de novo design of protein hetero-oligomers with three or more distinct chains with nearly identical structures is a challenging unsolved problem because it requires the accurate design of multiple protein-protein interfaces simultaneously. Here, we describe a divide-and-conquer approach that breaks the multiple-interface design challenge into a set of more tractable symmetric single-interface redesign tasks, followed by structural recombination of the validated homo-oligomers into pseudosymmetric hetero-oligomers. Starting from de novo designed circular homo-oligomers composed of 9 or 24 tandemly repeated units, we redesigned the inter-subunit interfaces to generate 19 new homo-oligomers and structurally recombined them to make 24 new hetero-oligomers, including ABC heterotrimers, A2B2 heterotetramers, and A3B3 and A2B2C2 heterohexamers which assemble with high structural specificity. The symmetric homo-oligomers and pseudosymmetric hetero-oligomers generated for each system have identical or nearly identical backbones, and hence are ideal building blocks for generating and functionalizing larger symmetric and pseudosymmetric assemblies.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"256 1","pages":""},"PeriodicalIF":16.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142841645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}