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Title: Structural basis for activity of TRIC counter-ion channels in calcium release

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [2];  [3];  [1];  [1];  [1];  [2];  [1];  [4];  [5];  [6];  [7];  [7];  [8];  [1]
  1. Chinese Academy of Sciences (CAS), Beijing (China). State Key Lab. of Molecular Developmental Biology. Inst. of Genetics and Developmental Biology; CAS Center for Excellence in Biomacromolecules, Beijing (China); Univ. of Chinese Academy of Sciences, Beijing (China)
  2. Chinese Academy of Sciences (CAS), Beijing (China). State Key Lab. of Molecular Developmental Biology. Inst. of Genetics and Developmental Biology; CAS Center for Excellence in Biomacromolecules, Beijing (China)
  3. Xi’an Jiaotong Univ. (China). The Key Lab. of Biomedical Information Engineering of Ministry of Education. Inst. of Health and Rehabilitation Science. School of Life Science and Technology
  4. New York Univ. (NYU), NY (United States). Dept. of Biology
  5. Brookhaven National Lab. (BNL), Upton, NY (United States). Biology Dept.
  6. Columbia Univ., New York, NY (United States). Dept. of Physiology and Cellular Biophysics
  7. Chinese Academy of Sciences (CAS), Beijing (China). State Key Lab. of Molecular Developmental Biology. Inst. of Genetics and Developmental Biology
  8. Columbia Univ., New York, NY (United States). Dept. of Physiology and Cellular Biophysics. Dept. of Biochemistry and Molecular Biophysics
+ Show Author Affiliations

Trimeric intracellular cation (TRIC) channels are thought to provide counter-ion currents that facilitate the active release of Ca2+ from intracellular stores. TRIC activity is controlled by voltage and Ca2+ modulation, but underlying mechanisms have remained unknown. We describe high-resolution crystal structures of vertebrate TRIC-A and TRIC-B channels, both in Ca2+-bound and Ca2+-free states, and we analyze conductance properties in structure-inspired mutagenesis experiments. The TRIC channels are symmetric trimers, wherein we find a pore in each protomer that is gated by a highly conserved lysine residue. In the resting state, Ca2+ binding at the luminal surface of TRIC-A, on its threefold axis, stabilizes lysine blockage of the pores. During active Ca2+ release, luminal Ca2+ depletion removes inhibition to permit the lysine-bearing and voltage-sensing helix to move in response to consequent membrane hyperpolarization. Diacylglycerol is found at interprotomer interfaces, suggesting a role in metabolic control.

Research Organization:
Brookhaven National Lab. (BNL), Upton, NY (United States); New York Univ. (NYU), NY (United States); Columbia Univ., New York, NY (United States); Chinese Academy of Sciences (CAS), Beijing (China); University of Chinese Academy of Sciences, Beijing (China); Xi’an Jiaotong Univ. (China)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH); National Key Research and Development Program of China; Chinese Academy of Sciences Strategic Priority Research Program; National Natural Science Foundation of China (NSFC); Office of Global Experts Recruitment; Xi’an Jiaotong University; State Key Laboratory of Molecular Developmental Biology
Grant/Contract Number:
SC0012704; R01GM106037; GM 107462; P41 GM116799; 2016YFA0500503; 2015CB910102; XDB08020301; 31872721; 31470728; 31322005; 31728010; 11672226; 2018-MDB-KF-02
OSTI ID:
1498857
Report Number(s):
BNL-211344-2019-JAAM
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Vol. 116, Issue 10; ISSN 0027-8424
Publisher:
National Academy of SciencesCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 16 works
Citation information provided by
Web of Science

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Cited By (1)

Enhanced activity of multiple TRIC‐B channels: an endoplasmic reticulum/sarcoplasmic reticulum mechanism to boost counterion currents journal April 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
counter-ion mechanism
Ca2+ modulation
lipid modulation
X-ray crystallography
electrophysiology