TY - JOUR
T1 - Candidate amino acids involved in H+ gating of acid-sensing ion channel 1a
AU - Paukert, Martin
AU - Chen, Xuanmao
AU - Polleichtner, Georg
AU - Schindelin, Hermann
AU - Gründer, Stefan
PY - 2008/1/4
Y1 - 2008/1/4
N2 - Acid-sensing ion channels are ligand-gated cation channels, gated by extracellular H+. H+ is the simplest ligand possible, and whereas for larger ligands that gate ion channels complex binding sites in the three-dimensional structure of the proteins have to be assumed, H+ could in principle gate a channel by titration of a single amino acid. Experimental evidence suggests a more complex situation, however. For example, it has been shown that extracellular Ca2+ ions compete with H +; probably Ca2+ ions bound to the extracellular loop of ASICs stabilize the closed state of the channel and have to be displaced before the channel can open. In such a scheme, amino acids contributing to Ca 2+ binding would also be candidates contributing to H+ gating. In this study we systematically screened more than 40 conserved, charged amino acids in the extracellular region of ASIC1a for a possible contribution to H+ gating. We identified four amino acids where substitution strongly affects H+ gating: Glu63, His72/ His73, and Asp78. These amino acids are highly conserved among H+-sensitive ASICs and are candidates for the "H + sensor" of ASICs.
AB - Acid-sensing ion channels are ligand-gated cation channels, gated by extracellular H+. H+ is the simplest ligand possible, and whereas for larger ligands that gate ion channels complex binding sites in the three-dimensional structure of the proteins have to be assumed, H+ could in principle gate a channel by titration of a single amino acid. Experimental evidence suggests a more complex situation, however. For example, it has been shown that extracellular Ca2+ ions compete with H +; probably Ca2+ ions bound to the extracellular loop of ASICs stabilize the closed state of the channel and have to be displaced before the channel can open. In such a scheme, amino acids contributing to Ca 2+ binding would also be candidates contributing to H+ gating. In this study we systematically screened more than 40 conserved, charged amino acids in the extracellular region of ASIC1a for a possible contribution to H+ gating. We identified four amino acids where substitution strongly affects H+ gating: Glu63, His72/ His73, and Asp78. These amino acids are highly conserved among H+-sensitive ASICs and are candidates for the "H + sensor" of ASICs.
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U2 - 10.1074/jbc.M706811200
DO - 10.1074/jbc.M706811200
M3 - Article
C2 - 17981796
AN - SCOPUS:38049100869
VL - 283
SP - 572
EP - 581
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 1
ER -