Structural basis for the regulation of inositol trisphosphate receptors by Ca2+ and IP3

Nature Structural & Molecular Biology
Navid Paknejad, Richard K Hite

Abstract

Inositol trisphosphate receptors (IP3Rs) are ubiquitous Ca2+-permeable channels that mediate release of Ca2+ from the endoplasmic reticulum, thereby regulating numerous processes including cell division, cell death, differentiation and fertilization. IP3Rs are jointly activated by inositol trisphosphate (IP3) and their permeant ion, Ca2+. At high concentrations, however, Ca2+ inhibits activity, ensuring precise spatiotemporal control over intracellular Ca2+. Despite extensive characterization of IP3R, the mechanisms through which these molecules control channel gating have remained elusive. Here, we present structures of full-length human type 3 IP3Rs in ligand-bound and ligand-free states. Multiple IP3-bound structures demonstrate that the large cytoplasmic domain provides a platform for propagation of long-range conformational changes to the ion-conduction gate. Structures in the presence of Ca2+ reveal two Ca2+-binding sites that induce the disruption of numerous interactions between subunits, thereby inhibiting IP3R. These structures thus provide a mechanistic basis for beginning to understand the regulation of IP3R.

References

Apr 30, 1984·Biochemical and Biophysical Research Communications·E SuematsuH Kuriyama
Jan 1, 1995·Neuron·L Stehno-BittelD E Clapham
Jun 1, 1997·The EMBO Journal·G Hajnóczky, A P Thomas
Feb 28, 2001·The EMBO Journal·J S Marchant, I Parker
Mar 7, 2003·The Journal of Biological Chemistry·Keiko UchidaKatsuhiko Mikoshiba
Nov 1, 2003·The Journal of Biological Chemistry·Kozo HamadaKatsuhiko Mikoshiba
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
May 14, 2005·Journal of Structural Biology·Christian SulowayBridget Carragher
Sep 27, 2005·Journal of Structural Biology·David N Mastronarde
Apr 13, 2007·Physiological Reviews·J Kevin FoskettDon-On Daniel Mak
Nov 14, 2007·The Journal of General Physiology·Lucian IonescuDon-On Daniel Mak
Dec 17, 2009·Nature Structural & Molecular Biology·Axel KirchhoferUlrich Rothbauer
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Sep 17, 2010·The Journal of Biological Chemistry·Jenny ChanMitsuhiko Ikura
Aug 31, 2011·Proceedings of the National Academy of Sciences of the United States of America·Tadashi ShinoharaKatsuhiko Mikoshiba
Sep 6, 2011·Nature Structural & Molecular Biology·Chun-Chi LinZhe Lu
Mar 23, 2012·Biochemical Society Transactions·Michael J Berridge
Sep 17, 2013·ELife·Andrew MorinPiotr Sliz
Nov 12, 2013·Nature Methods·Alp KucukelbirHemant D Tagare
Dec 17, 2014·Advances in Biological Regulation·Katsuhiko Mikoshiba
Dec 17, 2014·Biochimica Et Biophysica Acta·Tamara VervloessemJan B Parys
Apr 18, 2015·Nucleic Acids Research·Alexey DrozdetskiyGeoffrey J Barton
May 10, 2015·Advances in Experimental Medicine and Biology·D Randall Armant
Aug 19, 2015·Journal of Structural Biology·Alexis Rohou, Nikolaus Grigorieff
Oct 13, 2015·Nature·Guizhen FanIrina I Serysheva
Feb 3, 2016·The Journal of Physiology·David L Prole, Colin W Taylor
Aug 12, 2016·Physiological Reviews·Michael J Berridge

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Citations

Sep 20, 2018·The Journal of Biological Chemistry·Suresh K JosephGyörgy Hajnóczky
Feb 13, 2019·Cold Spring Harbor Perspectives in Biology·David L Prole, Colin W Taylor
Jul 7, 2019·Nature·Deshun GongNieng Yan
Dec 17, 2019·The Journal of General Physiology·Toshiko YamazawaMasamitsu Iino
Dec 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Ximin ChiNieng Yan
Nov 16, 2019·Annual Review of Physiology·Kozo Hamada, Katsuhiko Mikoshiba
Sep 11, 2019·Cold Spring Harbor Perspectives in Biology·Hristina IvanovaGeert Bultynck
Aug 20, 2019·Nature Communications·Sunghoon KimYouxing Jiang
Jul 17, 2020·Open Biology·Paula SteinCarmen J Williams
Sep 20, 2020·Annals of Clinical and Translational Neurology·Julius RönkköEmil Ylikallio
Nov 25, 2018·Cell Research·Guizhen FanIrina I Serysheva
Mar 21, 2019·Annual Review of Biomedical Engineering·Jana OgnjenovićSriram Subramaniam
Dec 16, 2018·Journal of Cell Science·Ana M Rossi, Colin W Taylor
Apr 16, 2020·Journal of Clinical Medicine·Jessica GambardellaGaetano Santulli
Dec 6, 2020·International Journal of Molecular Sciences·Xiaoning ZhangXuhui Zeng
Jan 30, 2021·Frontiers in Cell and Developmental Biology·Aurora Gil-HernándezAlejandro Silva-Palacios
Mar 13, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Björn-Philipp DiercksMalene Brohus
May 27, 2021·Communications Biology·Mariah R BakerIrina I Serysheva
Jul 20, 2021·Physiological Reviews·Kellie A Woll, Filip Van Petegem
Aug 6, 2021·Nature·Josefina Del MármolVanessa Ruta
Aug 6, 2019·Current Opinion in Structural Biology·Lejla Zubcevic, Seok-Yong Lee

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Datasets Mentioned

BETA
EMD-

Methods Mentioned

BETA
gel-filtration
size-exclusion chromatography

Software Mentioned

cisTEM
space
UCSF Chimera
ResMap
Motioncor2
Jpred4
PyMOL
real
Rosetta
Coot

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