Structure of a volume-regulated anion channel of the LRRC8 family

Nature
Dawid DenekaRaimund Dutzler

Abstract

Volume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family that co-assemble to form hexameric complexes. Here, using cryo-electron microscopy and X-ray crystallography, we determine the structure of a homomeric channel of the obligatory subunit LRRC8A. This protein conducts ions and has properties in common with endogenous heteromeric channels. Its modular structure consists of a transmembrane pore domain followed by a cytoplasmic leucine-rich repeat domain. The transmembrane domain, which is structurally related to connexin proteins, is wide towards the cytoplasm but constricted on the outside by a structural unit that acts as a selectivity filter. An excess of basic residues in the filter and throughout the pore attracts anions by electrostatic interaction. Our work reveals the previously unknown architecture of volume-regulated anion channels and their mechanism of selective anion conduction.

References

May 1, 1994·The Journal of General Physiology·B NiliusG Droogmans
Jan 1, 1994·The American Journal of Physiology·H Pasantes-MoralesJ Morán
Dec 1, 1996·Journal of Molecular Graphics·O S SmartM S Sansom
Jan 1, 1997·Progress in Biophysics and Molecular Biology·B NiliusG Droogmans
Oct 6, 2000·Biochimica Et Biophysica Acta·A Bryan-SisnerosP Doroshenko
Oct 24, 2002·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsThomas C Terwilliger
Dec 9, 2003·The Journal of Clinical Investigation·Akihisa SawadaJunichi Hara
Mar 23, 2004·Biochimica Et Biophysica Acta·Gary S GoldbergPeter R Brink
Jul 21, 2004·Journal of Computational Chemistry·Eric F PettersenThomas E Ferrin
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jul 28, 2005·Protein Science : a Publication of the Protein Society·Pavel Strop, Axel T Brunger
Sep 27, 2005·Journal of Structural Biology·David N Mastronarde
Oct 3, 2006·Journal of Structural Biology·J Bernard Heymann, David M Belnap
Apr 15, 2008·Cellular and Molecular Life Sciences : CMLS·J BellaS C Lovell
Jan 8, 2009·Physiological Reviews·Else K HoffmannStine F Pedersen
Apr 3, 2009·Nature·Shoji MaedaTomitake Tsukihara
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Dec 1, 2009·Nature·Alexander I SobolevskyEric Gouaux
Dec 25, 2010·Cell·Edward L HuttlinSteven P Gygi
Mar 18, 2011·Biochemistry·Eric R Geertsma, Raimund Dutzler
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Garib N MurshudovAlexei A Vagin
Apr 26, 2012·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Federico Abascal, Rafael Zardoya
May 4, 2012·Nucleic Acids Research·Karel BerkaMichal Otyepka
Jul 31, 2012·Nature Methods·Sjors H W Scheres, Shaoxia Chen
Sep 25, 2012·Journal of Structural Biology·Sjors H W Scheres
Nov 29, 2012·Journal of Proteome Research·Houjiang ZhouShabaz Mohammed
Aug 21, 2013·Journal of Structural Biology·Giovanni CardoneAlasdair C Steven
Sep 12, 2013·Protein Expression and Purification·David L HackerFlorian M Wurm
May 2, 2014·The Journal of Biological Chemistry·Clarissa C LeeHidde L Ploegh
May 2, 2014·Nucleic Acids Research·Marco BiasiniTorsten Schwede
Aug 31, 2014·The Journal of Physiology·María C Hyzinski-GarcíaAlexander A Mongin
Dec 31, 2014·Nature Methods·Jianyi YangYang Zhang
Jan 24, 2015·Acta Crystallographica. Section D, Biological Crystallography·Alan BrownGarib Murshudov
Aug 19, 2015·Journal of Structural Biology·Alexis Rohou, Nikolaus Grigorieff
Jan 8, 2016·Pflügers Archiv : European journal of physiology·Stine F PedersenBernd Nilius
Jan 13, 2016·Nature Communications·Brad C BennettMark Yeager

❮ Previous
Next ❯

Citations

Jun 9, 2018·The Journal of Biological Chemistry·Jennifer C LückThomas J Jentsch
Jun 22, 2018·The Journal of Biological Chemistry·Pingzheng ZhouThomas J Jentsch
Sep 27, 2018·Experimental Dermatology·Janina TrotheTorsten Ertongur-Fauth
Apr 6, 2019·Acta Crystallographica. Section D, Structural Biology·Shibom BasuVincent Olieric
Jul 7, 2019·Scientific Reports·Anna L EppLeigh Anne Swayne
Dec 1, 2019·The Journal of Physiology·Pablo S Gaete, Jorge E Contreras
Feb 23, 2020·Bioscience, Biotechnology, and Biochemistry·Funong LuoMingzhou Li
Jan 29, 2020·The Journal of Biological Chemistry·Patrick J DunnSusumu Tomita
Jun 20, 2020·Protein Science : a Publication of the Protein Society·Weixin YangXuejun C Zhang
Nov 8, 2019·Biochemical Society Transactions·Mauricio Di Fulvio, Lydia Aguilar-Bryan
May 22, 2019·Adipocyte·Susheel K GunasekarRajan Sah
Aug 23, 2019·Scientific Reports·Andreas SchedlbauerSilvia Dossena
Aug 29, 2020·Acta Pharmacologica Sinica·Zheng-Wei LuoHong-Shuo Sun
Jan 18, 2019·The Journal of General Physiology·Kevin StrangeJerod S Denton
Dec 1, 2018·Nature Communications·Xin LiuLinfeng Sun
Mar 21, 2019·Annual Review of Biomedical Engineering·Jana OgnjenovićSriram Subramaniam
Aug 22, 2018·Nature Structural & Molecular Biology·Go KasuyaOsamu Nureki
Mar 8, 2019·Cancers·Martino CaramiaLuigi Catacuzzeno
Apr 26, 2019·IUBMB Life·Jamshid TabeshpourAmirhossein Sahebkar
Jan 29, 2020·Nature Structural & Molecular Biology·Johanna L SyrjanenHiro Furukawa
Jun 27, 2019·American Journal of Physiology. Cell Physiology·Yani LiuHailin Zhang
Feb 26, 2020·Science Advances·Batuujin BurendeiAtsunori Oshima
Mar 2, 2019·International Journal of Molecular Sciences·Xabier Elorza-VidalRaúl Estévez
Mar 22, 2019·Cancers·Karl KunzelmannRainer Schreiber
Jul 5, 2019·Scientific Reports·Guy M LenkJacob O Kitzman
May 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Muhammad Murtaza Hassan, Olasunkanmi O Olaoye
Jul 31, 2019·Nature Methods·Sai Raghavendra Maddhuri Venkata SubramaniyaDaisuke Kihara
Apr 2, 2020·Nature Structural & Molecular Biology·Zengqin DengPeng Yuan
Oct 20, 2020·The Journal of General Physiology·Pablo S GaeteJorge E Contreras
Oct 31, 2020·Clinical and Experimental Pharmacology & Physiology·Nargiza M ChorievaRavshan Z Sabirov
Dec 8, 2020·Frontiers in Cell and Developmental Biology·Michael KittlMartin Jakab
Dec 19, 2020·Frontiers in Cell and Developmental Biology·Raquel CenteioKarl Kunzelmann

❮ Previous
Next ❯

Datasets Mentioned

BETA
EMD-4362

Methods Mentioned

BETA
X-ray
transfection
size
light scattering
transfections

Software Mentioned

GraphPad
Phenix
SWISS
Prism
BlocRes
Clampfit
Coot
MotionCor2
MSMS
CHARMM36

Related Concepts

Related Feeds

Cardiac Conduction System

The cardiac conduction system is a specialized tract of myocardial cells responsible for maintaining normal cardiac rhythm. Discover the latest research on the cardiac conduction system here.

Related Papers

Pflügers Archiv : European journal of physiology
Thomas J JentschFelizia K Voss
BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology
Federico Abascal, Rafael Zardoya
Progress in Biophysics and Molecular Biology
Bernd NiliusG Droogmans
© 2022 Meta ULC. All rights reserved