Structural plasticity of human leptin binding to its receptor LepR

作     者：Yufeng Xie Xiaoxiong Li Jianxun Qi Guijun Shang Defen Lu George Fu Gao 

作者机构：CAS Key Laboratory of Pathogen Microbiology and ImmunologyInstitute of MicrobiologyChinese Academy of SciencesBeijingChina Department of Basic Medical SciencesSchool of MedicineTsinghua UniversityBeijingChina Shanxi Academy of Advanced Research and InnovationShanxiChina Shanxi Provincial Key Laboratory for Major Infectious Disease ResponseShanxiChina College of Life SciencesShanxi Agricultural UniversityShanxiChina 

出 版 物：《hLife》 (健康科学（英文）)

年 卷 期：2023年第1卷第2期

页      面：115-123页

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：sup-ported by the National Key Research and Development Program of China (grant numbers 2020YFA0509202) 

主　　题：LepR leptin signaling cryo-electron microscopy(cryo-EM) 

摘      要：Leptin receptor(LepR)signaling plays an essential role in balancing food intake and energy *** architec-ture of LepR signaling assembly is critical for its *** this study,we determined the structures of three distinct conformations of human leptin–LepR using cryo-electron microscopy at resolutions of 3.88,3.77,and 3.58Å.Both 2:2 and 3:3 stoichiometric assemblies were observed,and the complexes exhibited asymmetric open ***-tin undergoes substantial rearrangement of its flexible regions to accommodate binding to *** assembled leptin–LepR complexes connect through a“hand-in-hand*** open,interlocked 3:3 trimeric assembly results from the engagement of a third leptin–LepR heterodimer with a 2:2 *** asymmetric geometry of LepR is substantially distinct from that of other gp130 cytokine homologs,and that may be due to the twisted and rigid interface between the D3 and D4 *** results highlight the distinct engagement of leptin with LepR and provide important insights into the structural plasticity of LepR-signaling assemblies.