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

Cheng Ma ¹Yanping Luo ²Congyi Zhang ²Cheng Cheng ²Ning Hua ²Xiaocao Liu ²Jianan Wu ²Luying Qin ²Peilin Yu ³Jianhong Luo ⁴Fan Yang ⁵Lin-Hua Jiang ⁶Guojie Zhang ⁷Wei Yang⁸

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作者信息

1. 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
2. Department of Biophysics and Department of Neurosurgery,The Fourth Affiliated Hospital,Zhejiang University School of Medicine,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;Henan Collaborative Innovation Center of Prevention and Treatment of Mental Disorder,The Second Affiliated Hospital of Xinxiang Medical University,Xinxiang 453004,China
7. Evolutionary & Organismal Biology Research Center,School of Medicine,Zhejiang University,Hangzhou 310058,China
8. Department of Biophysics and Department of Neurosurgery,The Fourth Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310058,China;GuiZhou University Medical College,Guiyang 550025,China
折叠

Abstract

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.

Key words

TRPM2 channel/Activation mode/Molecular evolution

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基金项目

National Natural Science Foundation of China(82030108)

National Natural Science Foundation of China(31872796)

National Natural Science Foundation of China(32071102)

National Natural Science Foundation of China(32000707)

Zhejiang Provincial Natural Science Foundation of China(LD24H090004)

Zhejiang Provincial Natural Science Foundation of China(R16H090001)

Zhejiang Provincial Natural Science Foundation of China(LQ20H160039)

Zhejiang Provincial Natural Science Foundation of China(LTY21H160003)

Zhejiang Provincial Natural Science Foundation of China(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)

East-West Cooperation Project(2019BFH02003)

MOE Frontier Science Center for Brain Science & Brain-Machine Integration,Zhejiang University()

出版年

2024

科学通报(英文版)

中国科学院

科学通报(英文版)

CSTPCD

ISSN：1001-6538

参考文献量1

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