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

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

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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 acti-vated 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 gat-ing pattern has also evolved,from one Ca2+-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 activa-tion mode evolved through at least three identifiable stages in the past billion years from simple to com-plicated and coordinated.Such findings benefit the evolutionary investigations of other channels and proteins.

TRPM2 channelActivation modeMolecular evolution

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

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Department of Biophysics and Department of Neurosurgery,The Fourth Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China

Protein Facility,Core Facilities,Zhejiang University School of Medicine,Zhejiang University,Hangzhou 310058,China

Department of Toxicology,and Department of Medical Oncology of The Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China

Department of Neurobiology,Affiliated Mental Health Center,College of Brain Science and Brain Medicine,Zhejiang University School of Medicine,Hangzhou 310058,China

Department of Biophysics,and Kidney Disease Center of the First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China

Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province,and Department of Physiology and Pathophysiology,Xinxiang Medical University,Xinxiang 453004,China

Henan Collaborative Innovation Center of Prevention and Treatment of Mental Disorder,The Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453004,China

Evolutionary & Organismal Biology Research Center,School of Medicine,Zhejiang University,Hangzhou 310058,China

GuiZhou University Medical College,Guiyang 550025,China

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National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaZhejiang Provincial Natural Science Foundation of ChinaZhejiang Provincial Natural Science Foundation of ChinaZhejiang Provincial Natural Science Foundation of ChinaZhejiang Provincial Natural Science Foundation of ChinaZhejiang Provincial Natural Science Foundation of ChinaNational Major Scientific and Technological Special Project for"Significant New Drugs Development"Zhejiang Association for Science and Technology Talent Cultivation ProjectEast-West Cooperation ProjectMOE Frontier Science Center for Brain Science & Brain-Machine Integration,Zhejiang University

82030108318727963207110232000707LD24H090004R16H090001LQ20H160039LTY21H160003LY19B0200132018ZX09711001-004-005CTZB-20200801272019BFH02003

2024

科学通报(英文版)
中国科学院

科学通报(英文版)

CSTPCD
ISSN:1001-6538
年,卷(期):2024.69(18)
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