Divalent cation and chloride ion sites of chicken acid sensing ion channel 1a elucidated by x-ray crystallography

PloS One
Nate Yoder, Eric Gouaux

Abstract

Acid sensing ion channels (ASICs) are proton-gated ion channels that are members of the degenerin/epithelial sodium channel superfamily and are expressed throughout central and peripheral nervous systems. ASICs have been implicated in multiple physiological processes and are subject to numerous forms of endogenous and exogenous regulation that include modulation by Ca2+ and Cl- ions. However, the mapping of ion binding sites as well as a structure-based understanding of the mechanisms underlying ionic modulation of ASICs have remained elusive. Here we present ion binding sites of chicken ASIC1a in resting and desensitized states at high and low pH, respectively, determined by anomalous diffraction x-ray crystallography. The acidic pocket serves as a nexus for divalent cation binding at both low and high pH, while we observe divalent cation binding within the central vestibule on the resting channel at high pH only. Moreover, neutralization of residues positioned to coordinate divalent cations via individual and combined Glu to Gln substitutions reduced, but did not extinguish, modulation of proton-dependent gating by Ca2+. Additionally, we demonstrate that anion binding at the canonical thumb domain site is state-dependent and ...Continue Reading

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Citations

Feb 23, 2020·Annual Review of Neuroscience·Peng JinYuh-Nung Jan
Nov 7, 2019·American Journal of Physiology. Cell Physiology·Benjamin P LüscherShmuel Muallem
Apr 15, 2021·The Journal of General Physiology·Zhuyuan ChenCecilia M Canessa

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Methods Mentioned

BETA
size-exclusion chromatography
x-ray crystallography

Software Mentioned

pClamp
XDS
PHASER
XSCALE
Coot
Phenix

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