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Crystal structure of acid-sensing ion channel in complex with psalmotoxin 1 at low pHCrystal structure of acid-sensing ion channel in complex with psalmotoxin 1 at low pH
Structural highlights
FunctionASIC1_CHICK Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride (By similarity).[1] Publication Abstract from PubMedAcid-sensing ion channels (ASICs) are voltage-independent, amiloride-sensitive channels involved in diverse physiological processes ranging from nociception to taste. Despite the importance of ASICs in physiology, we know little about the mechanism of channel activation. Here we show that psalmotoxin activates non-selective and Na(+)-selective currents in chicken ASIC1a at pH 7.25 and 5.5, respectively. Crystal structures of ASIC1a-psalmotoxin complexes map the toxin binding site to the extracellular domain and show how toxin binding triggers an expansion of the extracellular vestibule and stabilization of the open channel pore. At pH 7.25 the pore is approximately 10 A in diameter, whereas at pH 5.5 the pore is largely hydrophobic and elliptical in cross-section with dimensions of approximately 5 by 7 A, consistent with a barrier mechanism for ion selectivity. These studies define mechanisms for activation of ASICs, illuminate the basis for dynamic ion selectivity and provide the blueprints for new therapeutic agents. Structural plasticity and dynamic selectivity of acid-sensing ion channel-spider toxin complexes.,Baconguis I, Gouaux E Nature. 2012 Sep 20;489(7416):400-5. doi: 10.1038/nature11375. Epub 2012 Jul 29. PMID:22842900[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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