Structural heterogeneity of the ion and lipid channel TMEM16F.

ABSTRACT: Transmembrane protein 16 F (TMEM16F) is a Ca²⁺-activated homodimer which functions as an ion channel and a phospholipid scramblase. Despite the availability of several TMEM16F cryogenic electron microscopy (cryo-EM) structures, the mechanism of activation and substrate translocation remains controversial, possibly due to restrictions in the accessible protein conformational space. In this study, we use atomic force microscopy under physiological conditions to reveal a range of structurally and mechanically diverse TMEM16F assemblies, characterized by variable inter-subunit dimerization interfaces and protomer orientations, which have escaped prior cryo-EM studies. Furthermore, we find that Ca²⁺-induced activation is associated to stepwise changes in the pore region th

SUBMITTER: Ye Z 

PROVIDER: S-EPMC10761740 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature