Cryo-EM structure of the volume-regulated anion channel LRRC8D isoform identifies features important for substrate permeation

ABSTRACT: Members of the leucine-rich repeat-containing 8 (LRRC8) protein family, composed of the five LRRC8A-E isoforms, are pore-forming components of the volume-regulated anion channel (VRAC), which is activated by cell swelling and transports halide anions and small organic compounds. Despite the recent availability of the cryo-EM structures of homo-hexameric LRRC8A, the structural basis of how LRRC8 isoforms other than LRRC8A contribute to the functional diversity of VRAC has remained elusive. In this study, we confirmed the absence of LRRC8 isoforms in the purified HsLRRC8D using mass spectrometry, and the structure of the HsLRRC8D homomer was analyzed using the cryo-EM. This work provides structural insights into the functional diversity of the LRRC8 protein family.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Takehiro Suzuki  

LAB HEAD: Naoshi Dohmae

PROVIDER: PXD018780 | Pride | 2020-05-27

REPOSITORIES: Pride