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

Abstract

Tweety Homologs (TTYHs) are highly conserved membrane proteins, whose functions remain poorly understood. Here, the authors present the cryo-EM structures of murine TTYH2 and TTYH3 that form cis-dimers in the presence of Ca2+, whereas in the absence of Ca2+ TTYH2 adopts monomeric and trans-dimeric structures. The presented structures lack ion conducting pathways, which is consistent with results from electrophysiology measurements.