Structures of tweety homolog proteins TTYH2 and TTYH3 reveal a Ca²⁺-dependent switch from intra- to intermembrane dimerization.

ABSTRACT: Tweety homologs (TTYHs) comprise a conserved family of transmembrane proteins found in eukaryotes with three members (TTYH1-3) in vertebrates. They are widely expressed in mammals including at high levels in the nervous system and have been implicated in cancers and other diseases including epilepsy, chronic pain, and viral infections. TTYHs have been reported to form Ca²⁺- and cell volume-regulated anion channels structurally distinct from any characterized protein family with potential roles in cell adhesion, migration, and developmental signaling. To provide insight into TTYH family structure and function, we determined cryo-EM structures of Mus musculus TTYH2 and TTYH3 in lipid nanodiscs. TTYH2 and TTYH3 adopt a previously unobserved fold which includes an extended extracell

SUBMITTER: Li B 

PROVIDER: S-EPMC8617170 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature