Identification of a unique Ca²⁺-binding site in rat acid-sensing ion channel 3.

ABSTRACT: Acid-sensing ion channels (ASICs) evolved to sense changes in extracellular acidity with the divalent cation calcium (Ca²⁺) as an allosteric modulator and channel blocker. The channel-blocking activity is most apparent in ASIC3, as removing Ca²⁺ results in channel opening, with the site's location remaining unresolved. Here we show that a ring of rat ASIC3 (rASIC3) glutamates (Glu435), located above the channel gate, modulates proton sensitivity and contributes to the formation of the elusive Ca²⁺ block site. Mutation of this residue to glycine, the equivalent residue in chicken ASIC1, diminished the rASIC3 Ca²⁺ block effect. Atomistic molecular dynamic simulations corroborate the involvement of this acidic residue in forming a high-affinity Ca

SUBMITTER: Zuo Z 

PROVIDER: S-EPMC5970173 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature