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| 1 | Structural insights into the activation of ATM kinase显示文摘Dear Editor, ATM (ataxia telangiectasia-mutated) is a master regulator in response to DNA damage and activates downstream pathways involved in cell cycle checkpoints, DNA damage repair, transcription regulation, immune response, central nervous system development and metabolism.1,2 Loss of ATM activity in human results in the pleiotropic neurodegeneration disorder ataxia-telangiectasia (A-T) that is characterized by immunodeficiency, cancer predisposition, premature aging and insulin-resistant diabetes.3,4,5 Despite extensive studies over the past two decades,6,7 it remains controversial how ATM is activated. Particularly, whether ATM exists in a monomeric form, whether the monomer is more active than dimer, and how dimer-to-monomer transition affects the ATM kinase activity, remain controversial. | Jianxiong Xiao Mengjie Liu Yilun Qi Yuriy Chaban Chao Gao Beiqing Pan Yuan Tian Zishuo Yu Jie Li Peijun Zhang Yanhui Xu | 2019 | Cell Research2019，29，8： | 1 |
| 2 | Cryo-EM structure of SMG1–SMG8–SMG9 complex显示文摘Nonsense-mediated mRNA decay(NMD)targets premature stop codon(PTC)-containing mRNAs for rapid degradation,and is essential for mammalian embryonic development,brain development and modulation of the stress response.The key event in NMD is the SMG1-mediated phosphorylation of an RNA helicase UPF1 and SMG1 kinase activity is inhibited by SMG8 and SMG9 in an unknown mechanism.Here,we determined the cryo-EM structures of human SMG1 at 3.6Åresolution and the SMG1–SMG8–SMG9 complex at 3.4Åresolution,respectively.SMG8 has a C-terminal kinase inhibitory domain(KID),which covers the catalytic pocket and inhibits the kinase activity of SMG1.Structural analyses suggest that GTP hydrolysis of SMG9 would lead to a dramatic conformational change of SMG8–SMG9 and the KID would move away from the inhibitory position to restore SMG1 kinase activity.Thus,our structural and biochemical analyses provide a mechanistic understanding of SMG1–SMG8–SMG9 complex assembly and the regulatory mechanism of SMG1 kinase activity. | Li Zhu Liang Li Yilun Qi Zishuo Yu Yanhui Xu | 2019 | Cell Research2019，29，12： | 0 |
| 3 | Bioinspired polysaccharide-based nanocomposite membranes with robust wet mechanical properties for guided bone regeneration显示文摘Polysaccharide-based membranes with excellent mechanical properties are highly desired.However,severe mechanical deterioration under wet conditions limits their biomedical applications.Here,inspired by the structural heterogeneity of strong yet hydrated biological materials,we propose a strategy based on heterogeneous crosslink-and-hydration(HCH)of a molecule/nano dual-scale network to fabricate polysaccharide-based nanocomposites with robust wet mechanical properties.The heterogeneity lies in that the crosslink-and-hydration occurs in the molecule-network while the stress-bearing nanofiber-network remains unaffected.As one demonstration,a membrane assembled by bacterial cellulose nanofiber-network and Ca2+-crosslinked and hydrated sodium alginate molecule-network is designed.Studies show that the crosslinked-and-hydrated molecule-network restricts water invasion and boosts stress transfer of the nanofiber-network by serving as interfibrous bridge.Overall,the molecule-network makes the membrane hydrated and flexible;the nanofiber-network as stress-bearing component provides strength and toughness.The HCH dual-scale network featuring a cooperative effect stimulates the design of advanced biomaterials applied under wet conditions such as guided bone regeneration membranes. | Jian-Hong Xiao Zhen-Bang Zhang JiaHao Li Si-Ming Chen Huai-Ling Gao YinXiu Liao Lu Chen ZiShuo Wang YiFan Lu YuanZhen Hou HengAn Wu DuoHong Zou Shu-Hong Yu | 2024 | National Science Review2024，11，3： | 0 |
| 4 | Structure of human RNA polymerase Ⅲ elongation complex显示文摘RNA polymerase Ⅲ(Pol Ⅲ)transcribes essential structured small RNAs,such as tRNAs,5S rRNA and U6 snRNA.The transcriptional activity of Pol Ⅲ is tightly controlled and its dysregulation is associated with human diseases,such as cancer.Human Pol Ⅲ has two isoforms with difference only in one of its subunits RPC7(αandβ).Despite structural studies of yeast Pol Ⅲ,structure of human Pol Ⅲ remains unsolved.Here,we determined the structures of 17-subunit human Pol Ⅲαcomplex in the backtracked and post-translocation states,respectively.Human Pol Ⅲ contains a generally conserved catalytic core,similar to that of yeast counterpart,and structurally unique RPC3–RPC6–RPC7 heterotrimer and RPC10.The N-ribbon of TFIIS-like RPC10 docks on the RPC4–RPC5 heterodimer and the C-ribbon inserts into the funnel of Pol Ⅲ in the backtracked state but is more flexible in the post-translocation state.RPC7 threads through the heterotrimer and bridges the stalk and Pol Ⅲ core module.The winged helix 1 domain of RPC6 and the N-terminal region of RPC7αstabilize each other and may prevent Maf1-mediated repression of Pol Ⅲ activity.The C-terminal FeS cluster of RPC6 coordinates a network of interactions that mediate core–heterotrimer contacts and stabilize Pol Ⅲ.Our structural analysis sheds new light on the molecular mechanism of human Pol Ⅲα-specific transcriptional regulation and provides explanations for upregulated Pol Ⅲ activity in RPC7α-dominant cancer cells. | Liang Li Zishuo Yu Dan Zhao Yulei Ren Haifeng Hou Yanhui Xu | 2021 | Cell Research2021，31，7： | 0 |
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