Cryo-EM structures of an LRRC8 chimera with native functional properties reveal heptameric assembly.

ABSTRACT: Volume-regulated anion channels (VRACs) mediate volume regulatory Cl^- and organic solute efflux from vertebrate cells. VRACs are heteromeric assemblies of LRRC8A-E proteins with unknown stoichiometries. Homomeric LRRC8A and LRRC8D channels have a small pore, hexameric structure. However, these channels are either non-functional or exhibit abnormal regulation and pharmacology, limiting their utility for structure-function analyses. We circumvented these limitations by developing novel homomeric LRRC8 chimeric channels with functional properties consistent with those of native VRAC/LRRC8 channels. We demonstrate here that the LRRC8C-LRRC8A(IL1²⁵) chimera comprising LRRC8C and 25 amino acids unique to the first intracellular loop (IL1) of LRRC8A has a heptameric structur

SUBMITTER: Takahashi H 

PROVIDER: S-EPMC10049205 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature