Proline substitutions in the ASIC1 β11-12 linker slow desensitization.

ABSTRACT: Desensitization is a prominent feature of nearly all ligand gated ion channels. Acid-sensing ion channels (ASIC) undergo desensitization within hundreds of milliseconds to seconds upon continual extracellular acidification. The ASIC mechanism of desensitization is primarily due to the isomerization or "flipping" of a short linker joining the 11^th and 12^th beta sheets in the extracellular domain. In the resting and active states this β11-12 linker adopts an "upward" conformation while in the desensitized conformation the linker assumes a "downward" state. To accommodate this "downward" state, specific peptide bonds within the linker adopt either trans-like or cis-like conformations. Since proline-containing peptide bonds undergo cis-trans isomerization very slowly, we

SUBMITTER: Purohit R 

PROVIDER: S-EPMC11118455 | biostudies-literature | 2024 May

REPOSITORIES: biostudies-literature