Evolutionary trajectory of TRPM2 channel activation by adenosine diphosphate ribose and calcium  

腺苷二磷酸核糖和钙离子激活TRPM2通道的演化历程

作　　者：Cheng Ma Yanping Luo Congyi Zhang Cheng Cheng Ning Hua Xiaocao Liu Jianan Wu Luying Qin Peilin Yu Jianhong Luo Fan Yang Lin-Hua Jiang Guojie Zhang Wei Yang 马骋;骆燕萍;张聪毅;程澄;华宁;刘小草;吴佳男;覃露莹;余沛霖;罗建红;杨帆;江林华;张国捷;杨巍

机构地区：[1]Department of Biophysics and Department of Neurosurgery,The Fourth Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China [2]Protein Facility,Core Facilities,Zhejiang University School of Medicine,Zhejiang University,Hangzhou 310058,China [3]Department of Toxicology,and Department of Medical Oncology of The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China [4]Department of Neurobiology,Affiliated Mental Health Center,College of Brain Science and Brain Medicine,Zhejiang University School of Medicine,Hangzhou 310058,China [5]Department of Biophysics,and Kidney Disease Center of The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China [6]Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province,and Department of Physiology and Pathophysiology,Xinxiang Medical University,Xinxiang 453004,China [7]Henan Collaborative Innovation Center of Prevention and Treatment of Mental Disorder,The Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453004,China [8]Evolutionary&Organismal Biology Research Center,School of Medicine,Zhejiang University,Hangzhou 310058,China [9]GuiZhou University Medical College,Guiyang 550025,China

出　　处：《Science Bulletin》2024年第18期2892-2905,共14页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82030108,31872796,32071102,and 32000707);the Zhejiang Provincial Natural Science Foundation of China(LD24H090004,R16H090001,LQ20H160039,LTY21H160003,and LY19B020013);National Major Scientific and Technological Special Project for“Significant New Drugs Development”(2018ZX09711001-004-005);Zhejiang Association for Science and Technology Talent Cultivation Project(CTZB-2020080127);the East-West Cooperation Project(2019BFH02003);the MOE Frontier Science Center for Brain Science&Brain-Machine Integration,Zhejiang University。

摘　　要：Ion channel activation upon ligand gating triggers a myriad of biological events and,therefore,evolution of ligand gating mechanism is of fundamental importance.TRPM2,a typical ancient ion channel,is activated by adenosine diphosphate ribose(ADPR)and calcium and its activation has evolved from a simple mode in invertebrates to a more complex one in vertebrates,but the evolutionary process is still unknown.Molecular evolutionary analysis of TRPM2s from more than 280 different animal species has revealed that,the C-terminal NUDT9-H domain has evolved from an enzyme to a ligand binding site for activation,while the N-terminal MHR domain maintains a conserved ligand binding site.Calcium gating pattern has also evolved,from one Ca^(2+)-binding site as in sea anemones to three sites as in human.Importantly,we identified a new group represented by olTRPM2,which has a novel gating mode and fills the missing link of the channel gating evolution.We conclude that the TRPM2 ligand binding or activation mode evolved through at least three identifiable stages in the past billion years from simple to complicated and coordinated.Such findings benefit the evolutionary investigations of other channels and proteins.

关 键 词：TRPM2 channel Activation mode Molecular evolution 

分 类 号：Q75[生物学—分子生物学]