Search Menu
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information
Search Scholarly Publications

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

Abstract

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.

Authors:
 [1];  [2];  [2];  [3];  [1];  [1];  [1];  [2];  [1];  [4];  [5];  [6];  [7];  [7];  [8];  [1]
+ Show Author Affiliations
  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
Publication Date:
Research Org.:
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 Org.:
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
OSTI Identifier:
1498857
Report Number(s):
BNL-211344-2019-JAAM
Journal ID: ISSN 0027-8424
Grant/Contract Number:  
SC0012704; R01GM106037; GM 107462; P41 GM116799; 2016YFA0500503; 2015CB910102; XDB08020301; 31872721; 31470728; 31322005; 31728010; 11672226; 2018-MDB-KF-02
Resource Type:
Accepted Manuscript
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Volume: 116; Journal Issue: 10; Journal ID: ISSN 0027-8424
Publisher:
National Academy of Sciences
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; counter-ion mechanism; Ca2+ modulation; lipid modulation; X-ray crystallography; electrophysiology

Citation Formats

Wang, Xiao-hui, Su, Min, Gao, Feng, Xie, Wenjun, Zeng, Yang, Li, De-lin, Liu, Xue-lei, Zhao, Hong, Qin, Li, Li, Fei, Liu, Qun, Clarke, Oliver B., Lam, Sin Man, Shui, Guang-hou, Hendrickson, Wayne A., and Chen, Yu-hang. Structural basis for activity of TRIC counter-ion channels in calcium release. United States: N. p., 2019. Web. doi:10.1073/pnas.1817271116.
Copy to clipboard
Wang, Xiao-hui, Su, Min, Gao, Feng, Xie, Wenjun, Zeng, Yang, Li, De-lin, Liu, Xue-lei, Zhao, Hong, Qin, Li, Li, Fei, Liu, Qun, Clarke, Oliver B., Lam, Sin Man, Shui, Guang-hou, Hendrickson, Wayne A., & Chen, Yu-hang. Structural basis for activity of TRIC counter-ion channels in calcium release. United States. https://doi.org/10.1073/pnas.1817271116
Copy to clipboard
Wang, Xiao-hui, Su, Min, Gao, Feng, Xie, Wenjun, Zeng, Yang, Li, De-lin, Liu, Xue-lei, Zhao, Hong, Qin, Li, Li, Fei, Liu, Qun, Clarke, Oliver B., Lam, Sin Man, Shui, Guang-hou, Hendrickson, Wayne A., and Chen, Yu-hang. Fri . "Structural basis for activity of TRIC counter-ion channels in calcium release". United States. https://doi.org/10.1073/pnas.1817271116. https://www.osti.gov/servlets/purl/1498857.
Copy to clipboard
@article{osti_1498857,
title = {Structural basis for activity of TRIC counter-ion channels in calcium release},
author = {Wang, Xiao-hui and Su, Min and Gao, Feng and Xie, Wenjun and Zeng, Yang and Li, De-lin and Liu, Xue-lei and Zhao, Hong and Qin, Li and Li, Fei and Liu, Qun and Clarke, Oliver B. and Lam, Sin Man and Shui, Guang-hou and Hendrickson, Wayne A. and Chen, Yu-hang},
abstractNote = {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.},
doi = {10.1073/pnas.1817271116},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 10,
volume = 116,
place = {United States},
year = {Fri Feb 15 00:00:00 EST 2019},
month = {Fri Feb 15 00:00:00 EST 2019}
}
Copy to clipboard
Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
https://doi.org/10.1073/pnas.1817271116
Copyright Statement
Other availability
Search WorldCat Search WorldCat to find libraries that may hold this journal
Citation Metrics:
Cited by: 16 works
Citation information provided by
Web of Science
Save / Share:
Export Metadata
Save to My Library
You must Sign In or Create an Account in order to save documents to your library.

Works referenced in this record:

Calcium uptake and release modulated by counter-ion conductances in the sarcoplasmic reticulum of skeletal muscle
journal, March 1996

Blockade of cardiac sarcoplasmic reticulum K+ channel by Ca2+: two-binding-site model of blockade
journal, July 1991

TRIC-B Mutations Causing Osteogenesis Imperfecta
journal, January 2016

  • Ichimura, Atsuhiko; Takeshima, Hiroshi
  • Biological & Pharmaceutical Bulletin, Vol. 39, Issue 11
  • DOI: 10.1248/bpb.b16-00612

Mechanism of Inhibition of Cyclic Nucleotide–Gated Ion Channels by Diacylglycerol
journal, November 2000

  • Crary, Jennifer I.; Dean, Dylan M.; Nguitragool, Wang
  • The Journal of General Physiology, Vol. 116, Issue 6
  • DOI: 10.1085/jgp.116.6.755

Channel-mediated monovalent cation fluxes in isolated sarcoplasmic reticulum vesicles
journal, June 1984

Sarcoplasmic Reticulum Ca2+ Release Uses a Cascading Network of Intra-SR and Channel Countercurrents
journal, January 2018

Mice lacking the intracellular cation channel TRIC-B have compromised collagen production and impaired bone mineralization
journal, May 2016

The crystal structure of a voltage-gated sodium channel
journal, July 2011

  • Payandeh, Jian; Scheuer, Todd; Zheng, Ning
  • Nature, Vol. 475, Issue 7356
  • DOI: 10.1038/nature10238

Structural basis for conductance through TRIC cation channels
journal, May 2017

TRIC channels are essential for Ca2+ handling in intracellular stores
journal, July 2007

  • Yazawa, Masayuki; Ferrante, Christopher; Feng, Jue
  • Nature, Vol. 448, Issue 7149
  • DOI: 10.1038/nature05928

Pore architecture of TRIC channels and insights into their gating mechanism
journal, October 2016

  • Yang, Hanting; Hu, Miaohui; Guo, Jianli
  • Nature, Vol. 538, Issue 7626
  • DOI: 10.1038/nature19767

Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation
journal, October 2012

COBALT: constraint-based alignment tool for multiple protein sequences
journal, March 2007

Intracellular Calcium Release Channels Mediate Their Own Countercurrent: The Ryanodine Receptor Case Study
journal, October 2008

Crystal structures of the TRIC trimeric intracellular cation channel orthologues
journal, December 2016

  • Kasuya, Go; Hiraizumi, Masahiro; Maturana, Andrés D.
  • Cell Research, Vol. 26, Issue 12
  • DOI: 10.1038/cr.2016.140

The family of K 2P channels: salient structural and functional properties : The family of K
journal, January 2015

  • Feliciangeli, Sylvain; Chatelain, Frank C.; Bichet, Delphine
  • The Journal of Physiology, Vol. 593, Issue 12
  • DOI: 10.1113/jphysiol.2014.287268

Trimeric Intracellular Cation Channels and Sarcoplasmic/Endoplasmic Reticulum Calcium Homeostasis
journal, February 2014

TRIC-A Channels in Vascular Smooth Muscle Contribute to Blood Pressure Maintenance
journal, August 2011

Dynamic NHERF interaction with TRPC4/5 proteins is required for channel gating by diacylglycerol
journal, December 2016

  • Storch, Ursula; Forst, Anna-Lena; Pardatscher, Franziska
  • Proceedings of the National Academy of Sciences, Vol. 114, Issue 1
  • DOI: 10.1073/pnas.1612263114

A novel deletion mutation involving TMEM38B in a patient with autosomal recessive osteogenesis imperfecta
journal, July 2014

Bioinformatic Characterization of the Trimeric Intracellular Cation-Specific Channel Protein Family
journal, April 2011

Phosphoinositide Control of Membrane Protein Function: A Frontier Led by Studies on Ion Channels
journal, February 2015

Tracking the sarcoplasmic reticulum membrane voltage in muscle with a FRET biosensor
journal, June 2018

  • Sanchez, Colline; Berthier, Christine; Allard, Bruno
  • The Journal of General Physiology
  • DOI: 10.1085/jgp.201812035

Calcium Modulation of Single SR Potassium Channel Currents in Heart Muscle
journal, February 1994

  • Uehara, Akira; Yasukochi, Midori; Imanaga, Issei
  • Journal of Molecular and Cellular Cardiology, Vol. 26, Issue 2
  • DOI: 10.1006/jmcc.1994.1022

Ion- and water-binding sites inside an occluded hourglass pore of a trimeric intracellular cation (TRIC) channel
journal, April 2017

ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures
journal, July 2005

  • Landau, M.; Mayrose, I.; Rosenberg, Y.
  • Nucleic Acids Research, Vol. 33, Issue Web Server
  • DOI: 10.1093/nar/gki370

Ca 2+ Overload and Sarcoplasmic Reticulum Instability in tric-a Null Skeletal Muscle
journal, September 2010

  • Zhao, Xiaoli; Yamazaki, Daiju; Park, Ki Ho
  • Journal of Biological Chemistry, Vol. 285, Issue 48
  • DOI: 10.1074/jbc.M110.170084

Activation by intracellular calcium of a potassium channel in cardiac sarcoplasmic reticulum
journal, February 1991

  • Uehara, Akira; Yasukohchi, Midori; Ogata, Shigenori
  • Pfl�gers Archiv European Journal of Physiology, Vol. 417, Issue 6
  • DOI: 10.1007/BF00372965

Two novel mutations in TMEM38B result in rare autosomal recessive osteogenesis imperfecta
journal, February 2016

  • Lv, Fang; Xu, Xiao-jie; Wang, Jian-yi
  • Journal of Human Genetics, Vol. 61, Issue 6
  • DOI: 10.1038/jhg.2016.11

Essential role of the TRIC-B channel in Ca2+ handling of alveolar epithelial cells and in perinatal lung maturation
journal, June 2009

  • Yamazaki, D.; Komazaki, S.; Nakanishi, H.
  • Development, Vol. 136, Issue 14
  • DOI: 10.1242/dev.036798

TRIC-B channels display labile gating: evidence from the TRIC-A knockout mouse model
journal, March 2013

  • Venturi, Elisa; Matyjaszkiewicz, Antoni; Pitt, Samantha J.
  • Pflügers Archiv - European Journal of Physiology, Vol. 465, Issue 8
  • DOI: 10.1007/s00424-013-1251-y

Charade of the SR K+-Channel: Two Ion-Channels, TRIC-A and TRIC-B, Masquerade as a Single K+-Channel
journal, July 2010

Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana
journal, December 2015

  • Guo, Jiangtao; Zeng, Weizhong; Chen, Qingfeng
  • Nature, Vol. 531, Issue 7593
  • DOI: 10.1038/nature16446

Voltage-gated cation conductance channel from fragmented sarcoplasmic reticulum: Steady-state electrical properties
journal, March 1978

  • Miller, Christopher
  • The Journal of Membrane Biology, Vol. 40, Issue 1
  • DOI: 10.1007/BF01909736

No voltage change at skeletal muscle SR membrane during Ca 2+ release—just Mermaids on acid
journal, July 2018

Ionic selectivity, saturation, and block in a K+-selective channel from sarcoplasmic reticulum
journal, October 1980

Calcium Signaling
journal, December 2007

Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor
journal, March 2008

  • Mancia, Filippo; Assur, Zahra; Herman, Ariel G.
  • EMBO reports, Vol. 9, Issue 4
  • DOI: 10.1038/embor.2008.27

Calcium signalling: dynamics, homeostasis and remodelling
journal, July 2003

  • Berridge, Michael J.; Bootman, Martin D.; Roderick, H. Llewelyn
  • Nature Reviews Molecular Cell Biology, Vol. 4, Issue 7
  • DOI: 10.1038/nrm1155

Crystal Structure of a Mammalian Voltage-Dependent Shaker Family K+ Channel
journal, August 2005

    Sort by:
    [ × clear filter / sort ]

    Works referencing / citing this record:

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

    • O'Brien, Fiona; Eberhardt, David; Witschas, Katja
    • The Journal of Physiology, Vol. 597, Issue 10
    • DOI: 10.1113/jp277241
      Sort by:
      [ × clear filter / sort ]

      Similar Records in DOE PAGES and OSTI.GOV collections: