2024

最新文章

• Protein language models learn evolutionary statistics of interacting sequence motifs AI翻译
  作者：Zhang, Zhidian; Wayment-Steele, Hannah K.; Brixi, Garyk; Wang, Haobo; Kern, Dorothee; Ovchinnikov, Sergey
  作者单位：Harvard University; Massachusetts Institute of Technology (MIT); Swiss School of Public Health (SSPH+); Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; Brandeis University; Howard Hughes Medical Institute; Brandeis University; Harvard University; Harvard University
  摘要：Protein language models (pLMs) have emerged as potent tools for predicting and designing protein structure and function, and the degree to which these models fundamentally understand the inherent biophysics of protein structure stands as an open question. Motivated by a finding that pLM-based structure predictors erroneously predict nonphysical structures for protein isoforms, we investigated the nature of sequence context needed for contact predictions in the pLM Evolutionary Scale Modeling (...
• Substrate specificity controlled by the exit site of human P4-ATPases, revealed by de novo point mutations in neurological disorders AI翻译
  作者：Calianese, David C.; Noji, Tomoyasu; Sullivan, Jennifer A.; Schoch, Kelly; Shashi, Vandana; McNiven, Vanda; Ramos, Luiza Lorena Pires; Jordanova, Albena; Karteszi, Judit; Ishikita, Hiroshi; Nagata, Shigekazu
  作者单位：University of North Carolina; University of North Carolina Chapel Hill; University of Osaka; University of Tokyo; Duke University; University of Toronto; University Health Network Toronto; McMaster University; McMaster University Hospital; Flanders Institute for Biotechnology (VIB); University of Antwerp; Medical University Sofia
  摘要：The maintenance of lipid asymmetry on the plasma membrane is regulated by flippases, such as ATP8A2, ATP11A, and ATP11C, which translocate phosphatidylserine and phosphatidylethanolamine from the outer leaflet to the inner leaflet. We previously identified a patient- derived point mutation (Q84E) in ATP11A at the phospholipid entry site, which acquired the ability to flip phosphatidylcholine (PtdCho). This mutation led to elevated levels of sphingomyelin (SM) in the outer leaflet of the plasma...
• A protein phosphatase 1 specific phosphatase targeting peptide (PhosTAP) to identify the PP1 phosphatome AI翻译
  作者：Choy, Meng S.; Nguyen, Hieu T.; Kumar, Ganesan S.; Peti, Wolfgang; Kettenbach, Arminja N.; Page, Rebecca
  作者单位：Dartmouth College; Department of Biotechnology (DBT) India; National Institute of Immunology (NII)
  摘要：Phosphoprotein phosphatases (PPPs) are the key serine/threonine phosphatases that regulate all essential signaling cascades. In particular, Protein Phosphatase 1 (PP1) dephosphorylates similar to 80% of all ser/thr phosphorylation sites. Here, we developed a phosphatase targeting peptide (PhosTAP) that binds all PP1 isoforms and does so with a stronger affinity than any other known PP1 regulator. This PhosTAP can be used as a PP1 recruitment tool for Phosphorylation Targeting Chimera (PhosTAC)...
• CD4 T cells restricted to DRB1*15:01 recognize two Epstein-Barr virus glycoproteins capable of intracellular antigen presentation AI翻译
  作者：Drosu, Natalia; Anderson, Monique; Bilodeau, Philippe A.; Nishiyama, Shuhei; Mikami, Takahisa; Khoury, Natasha Bobrowski -; Cabot, Jackson; Housman, David; Levy, Michael
  作者单位：Harvard University; Harvard University Medical Affiliates; Massachusetts General Hospital; Harvard University; Harvard Medical School; Massachusetts Institute of Technology (MIT)
  摘要：Both genetic and environmental factors contribute to multiple sclerosis (MS) risk. Infection with the Epstein-Barr virus (EBV) is the strongest environmental risk factor, and HLA- DR15 is the strongest genetic risk factor for MS. We employed computational methods and in vitro assays for CD4 T cell activation to investigate the DR15- restricted response to EBV. Using a machine learning- based HLA ligand predictor, the EBV glycoprotein B (gB) was predicted to be enriched in epitopes restricted t...
• Lactylation of RNA m6A demethylase ALKBH5 promotes innate immune response to DNA herpesviruses and mpox virus AI翻译
  作者：Li, Wan; Zhou, Jing; Gu, Yang; Chen, Yuheng; Huang, Yiming; Yang, Jingxin; Zhu, Xiaojuan; Zhao, Kangchen; Yan, Qin; Zhao, Zongzheng; Li, Xiao; Chen, Guochun; Jia, Xuemei; Gao, Shou-Jiang; Lu, Chun
  作者单位：Nanjing Medical University; Nanjing Medical University; Nanjing Medical University; Jiangsu Provincial Center for Disease Control & Prevention; Chinese Academy of Agricultural Sciences; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh; Pennsylvania Commonwealth System of Higher Education (PCSHE); University of Pittsburgh
  摘要：RNA N 6- methyladenosine (m6A) demethylase AlkB homolog 5 (ALKBH5) plays a crucial role in regulating innate immunity. Lysine acylation, a widespread protein modification, influences protein function, but its impact on ALKBH5 during viral infections has not been well characterized. This study investigates the presence and regulatory mechanisms of a previously unidentified lysine acylation in ALKBH5 and its role in mediating m6A modifications to activate antiviral innate immune responses. We de...
• Helical coiled nucleosome chromosome architectures during cell cycle progression AI翻译
  作者：McDonald, Angus; Murre, Cornelis; Sedat, John W.
  作者单位：Boise State University; University of California System; University of California San Diego; University of California System; University of California San Francisco
  摘要：Recent studies showed an interphase chromosome architecture-a specific coiled nucleosome structure-derived from cryopreserved EM tomograms, and dispersed throughout the nucleus. The images were computationally processed to fill in the missing wedges of data caused by incomplete tomographic tilts. The resulting structures increased z- resolution enabling an extension of the proposed architecture to that of mitotic chromosomes. Here, we provide additional insights into the chromosome architectur...
• Histone modifications of circulating nucleosomes are associated with changes in cell- free DNA fragmentation patterns AI翻译
  作者：Bai, Jinyue; Jiang, Peiyong; Ji, Lu; Lam, W. K. Jacky; Zhou, Qing; Ma, Mary- Jane L.; Ding, Spencer C.; Ramakrishnan, Saravanan; Wan, Chun Wai; Yang, Tongxin Claire; Yukawa, Masashi; Chan, Rebecca W. Y.; Qiao, Rong; Yu, Stephanie C. Y.; Choy, L. Y. Lois; Shi, Yuwei; Wang, Zilong; Tam, Tommy H. C.; Law, Man Fai; Wong, Raymond S. M.; Wong, John; Chan, Stephen Lam; Wong, Grace L. H.; Wong, Vincent W. S.; Chan, K. C. Allen; Lo, Y. M. Dennis
  作者单位：Chinese University of Hong Kong; Chinese University of Hong Kong; Prince of Wales Hospital; Chinese University of Hong Kong; Prince of Wales Hospital; Chinese University of Hong Kong; Prince of Wales Hospital; Chinese University of Hong Kong; Prince of Wales Hospital; Chinese University of Hong Kong; Prince of Wales Hospital
  摘要：The analysis of tissues of origin of cell- free DNA (cfDNA) is of research and diagnostic interest. Many studies focused on bisulfite treatment or immunoprecipitation protocols to assess the tissues of origin of cfDNA. DNA loss often occurs during such processes. Fragmentomics of cfDNA molecules has uncovered a wealth of information related to tissues of origin of cfDNA. There is still much room for the development of tools for assessing contributions from various tissues into plasma using fra...
• Does the direct effect of friction increase continuously with absolute temperature? AI翻译
  作者：Barbot, Sylvain
  作者单位：University of Southern California
  摘要：Constitutive models of fault friction form the basis of physics-based simulations of seismic activity. A generally accepted framework for the slip-rate and state dependence of friction involves a thermally activated process, whereby the probability of slip along microasperities adheres to an Arrhenius law. This model, which has become widely adopted among experimentalists and theoreticians, predicts a continuous increase of the direct effect with absolute temperature, but is it observed experi...
• Closing the geologic carbon cycle AI翻译
  作者：Derry, Louis A.
  作者单位：Cornell University; Universite Paris Cite
  摘要：Estimates of sedimentary organic carbon burial fluxes based on inventory and isotope mass balance methods have been divergent. A new calculation of the isotope mass balance using a revised assessment of the inputs to the ocean- atmosphere system resolves the apparent discrepancy. Inputs include weathering of carbonate and old kerogen, geogenic methane oxidation, and volcanic and metamorphic degassing. Volcanic and metamorphic degassing comprise approximate to 23% of the total C input. Inputs f...
• Neurotransmitter release is triggered by a calcium- induced rearrangement in the Synaptotagmin-1/SNARE complex primary interface AI翻译
  作者：Toulme, Estelle; Lazaro, Andrea Salazar; Trimbuch, Thorsten; Rizo, Josep; Rosenmund, Christian
  作者单位：Free University of Berlin; Humboldt University of Berlin; Charite Universitatsmedizin Berlin; Free University of Berlin; Humboldt University of Berlin; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center; University of Texas System; University of Texas Southwestern Medical Center
  摘要：The Ca2+ sensor synaptotagmin-1 (Syt1) triggers neurotransmitter release together with the neuronal sensitive factor attachment protein receptor (SNARE) complex formed by syntaxin-1, SNAP25, and synaptobrevin. Moreover, Syt1 increases synaptic vesicle (SV) priming and impairs spontaneous vesicle release. The Syt1 C2B domain binds to the SNARE complex through a primary interface via two regions (I and II), but how exactly this interface mediates distinct functions of Syt1 and the mechanism unde...