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• TRAMP assembly alters the conformation and RNA binding of Mtr4 and Trf4-Air2 AI翻译
  作者：Denson, Joshua M.; Zhang, Naifu; Ball, Darby; Thompson, Kayla; Johnson, Sean J.; D'Arcy, Sheena
  作者单位：Utah System of Higher Education; Utah State University; University of Texas System; University of Texas Dallas; University of Colorado System; University of Colorado Boulder; Bristol-Myers Squibb
  摘要：The TRAMP complex contains two enzymatic activities essential for RNA processing upstream of the nuclear exosome. Within TRAMP, RNA is 3 ' ' polyadenylated by a subcomplex of Trf4/5 and Air1/2 and unwound 3 ' ' to 5 ' ' by Mtr4, a DExH helicase. The molecular mechanisms of TRAMP assembly and RNA shuffling between the two TRAMP catalytic sites are poorly understood. Here, we report solution hydrogen-deute- rium exchange data with thermodynamic and functional assays to uncover these mecha- nisms...
• Retinal ganglion cells encode the direction of motion outside their classical receptive field AI翻译
  作者：Riccitelli, Serena; Yaakov, Hadar; Heukamp, Alina S.; Ankri, Lea; Etzion, Michal Rivlin -
  作者单位：Weizmann Institute of Science
  摘要：Retinal ganglion cells (RGCs) typically respond to light stimulation over their spatially restricted receptive field. Using large- scale recordings in the mouse retina, we show that motion direction, in response to a stimulus crossing an area far beyond the classic receptive field. The extraclassical response arises via inputs from an asymmetric distal zone and is enhanced by desensitization mechanisms and an inherent DS component, creating a network of neurons responding to motion toward the ...
• Genesis and regulation of C- terminal cyclic imides from protein damage AI翻译
  作者：Xu, Wenqing; Zhao, Zhenguang; Su, Matthew; Jain, Atul D.; Lloyd, Hannah C.; Feng, Ethan Yang; Cox, Nick; Woo, Christina M.
  作者单位：Harvard University
  摘要：C- Terminal cyclic imides are posttranslational modifications that can arise from spontaneous intramolecular cleavage of asparagine or glutamine residues resulting in a form of irreversible protein damage. These protein damage events are recognized and removed by the E3 ligase substrate adapter cereblon (CRBN), indicating that these aging- related modifications may require cellular quality control mechanisms to prevent deleterious effects. However, the factors that determine protein or peptide...
• Synapse- specific catecholaminergic modulation of neuronal glutamate release AI翻译
  作者：Bakshinska, Dariya; Liu, William YuChen; Schultz, Ryan; Stowers, R. Steven; Hoagland, Adam; Cypranowska, Caroline; Stanley, Cherise; Younger, Susan H.; Newman, Zachary L.; Isacoff, Ehud Y.
  作者单位：Francis Crick Institute; University of Minnesota System; University of Minnesota Twin Cities; University of California System; University of California Berkeley; University of California System; University of California Berkeley; Montana State University System; Montana State University Bozeman; University of California System; University of California Berkeley; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory
  摘要：Norepinephrine in vertebrates and its invertebrate analog, octopamine, regulate the activity of neural circuits. We find that, when hungry, Drosophila larvae switch activcoincide with locomotion- driving bursts in type I glutamatergic MNs that converge on the same muscles. Optical quantal analysis across hundreds of synapses simultaneously reveals that octopamine potentiates glutamate release by tonic type Ib MNs, but not phasic type Is MNs, and occurs via the Gq- coupled octopamine receptor (...
• RAP-2 and CNH-MAP4 Kinase MIG-15 confer resistance in bystander epithelium to cell- fate transformation by excess Ras or Notch activity AI翻译
  作者：Fakieh, Razan A.; Reiner, David J.
  作者单位：Texas A&M University System; Imam Abdulrahman Bin Faisal University; Texas A&M University System; Texas A&M University College Station; Texas A&M Health Science Center
  摘要：Induction of cell fates by growth factors impacts many facets of developmental biology and disease. LIN-3/EGF induces the equipotent vulval precursor cells (VPCs) in Caenorhabditis elegans to assume the 3 & ring;-3 & ring;-2 & ring;-1 & ring;-2 & ring;-3 & ring; pattern of cell fates. 1 & ring; and 2 & ring; cells become specialized epithelia and undergo stereotyped series of cell divisions to form the vulva. Conversely, 3 & ring; cells are relatively quiescent and nonspecialized; they divide ...
• Inhibition of oxidative metabolism leads to p53 genetic inactivation and transformation in neural stem cells ( vol 112 , pg 105 , 2015) AI翻译
  作者：Henriquez, Nick, V; Betts, Joanne; Saxena, Jayeta; Minieri, Valentina; Karlsson, Anna; Martins, L. Miguel; Capasso, Melania; Nicotera, Pierluigi; Brandner, Sebastian; De Laurenzi, Vincenzo; Salomoni, Paolo; Bartesaghi, Stefano; Graziano, Vincenzo; Galavotti, Sara; Deli, A.
• Structural basis of nearest- neighbor cooperativity in the ring- shaped gene regulatory protein TRAP from protein engineering and cryo- EM AI翻译
  作者：Li, Weicheng; Yang, Haoyun; Stachowski, Kye; Norris, Andrew S.; Lichtenthal, Katie; Kelly, Skyler; Gollnick, Paul; Wysocki, Vicki H.; Foster, Mark P.
  作者单位：University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; University System of Ohio; Ohio State University; State University of New York (SUNY) System; University at Buffalo, SUNY; University System of Ohio; Ohio State University
  摘要：The homo- dodecameric ring- shaped trp RNA binding attenuation protein (TRAP) from Alkalihalobacillus halodurans (Aha) binds up to twelve tryptophan ligands (Trp) and becomes activated to bind a specific sequence in the 5' leader region of the trp operon mRNA, thereby downregulating biosynthesis of Trp. Thermodynamic measurements of Trp binding have revealed a range of cooperative behavior for different TRAP variants, even if the averaged apparent affinities for Trp have been found to be simil...
• Topological confinement by a membrane anchor suppresses phase separation into protein aggregates: Implications for prion diseases AI翻译
  作者：Gogte, Kalpshree; Mamashli, Fatemeh; Herrera, Maria Georgina; Kriegler, Simon; Bader, Verian; Kamps, Janine; Grover, Prerna; Winter, Roland; Winklhofer, Konstanze F.; Tatzelt, Joerg
  作者单位：Ruhr University Bochum; Ruhr University Bochum; Dortmund University of Technology; Ruhr University Bochum
  摘要：Protein misfolding and aggregation are a hallmark of various neurodegenerative disorders. However, the underlying mechanisms driving protein misfolding in the cellular context are incompletely understood. Here, we show that the two- dimensional confinement imposed by a membrane anchor stabilizes the native protein conformation and suppresses liquid-liquid phase separation (LLPS) and protein aggregation. Inherited prion diseases in humans and neurodegeneration in transgenic mice are linked to t...
• Tamsulosin ameliorates bone loss by inhibiting the release of Cl- through wedging into an allosteric site of TMEM16A AI翻译
  作者：Li, Shiliang; Sun, Weijia; Li, Shuang; Zhu, Lili; Guo, Shuai; He, Jiaqi; Li, Yuheng; Tian, Chaoquan; Zhao, Zhenjiang; Yu, Tao; Li, Jianwei; Zhang, Yiqing; Hai, Youlong; Wang, Jiawen; Zheng, Yongjun; Wang, Rui; Hu, Xiaoyong; Ling, Shukuan; Li, Honglin; Li, Yingxian
  作者单位：East China Normal University; East China University of Science & Technology; Fudan University; Beijing Institute of Technology; Hebei University; Shanghai Jiao Tong University; Oujiang Laboratory; Lingang Laboratory
  摘要：TMEM16A, a key calcium- activated chloride channel, is crucial for many physiological and pathological processes such as cancer, hypertension, and osteoporosis, etc. However, the regulatory mechanism of TMEM16A is poorly understood, limiting the discovery of effective modulators. Here, we unveil an allosteric gating mechanism by presenting a high- resolution cryo-EM structure of TMEM16A in complex with a channel inhibitor that we identified, Tamsulosin, which is resolved at 2.93 & Aring;. Tams...
• Learning the language of antibody hypervariability AI翻译
  作者：Singh, Rohit; Im, Chiho; Qiu, Yu; Mackness, Brian; Gupta, Abhinav; Joren, Taylor; Sledzieski, Samuel; Erlach, Lena; Wendt, Maria; Nanfack, Yves Fomekong; Bryson, Bryan; Berger, Bonnie
  作者单位：Massachusetts Institute of Technology (MIT); Sanofi-Aventis; Sanofi USA; Sanofi-Aventis; Sanofi USA; Swiss Federal Institutes of Technology Domain; ETH Zurich; Massachusetts Institute of Technology (MIT); Massachusetts Institute of Technology (MIT)
  摘要：Protein language models (PLMs) have demonstrated impressive success in modeling proteins. However, general-purpose foundational PLMs have limited performance in modeling antibodies due to the latter's hypervariable regions, which do not conform to the evolutionary conservation principles that such models rely on. In this study, we propose a transfer learning framework called Antibody MutagenesisAugmented Processing (AbMAP), which fine-tunes foundational models for antibody- sequence inputs by ...