Cryo-EM structure of mouse TRPML2 in lipid nanodiscs.

ABSTRACT: In mammalians, transient receptor potential mucolipin ion channels (TRPMLs) exhibit variable permeability to cations such as Ca²⁺, Fe²⁺, Zn²⁺, and Na⁺ and can be activated by the phosphoinositide PI(3,5)P2 in the endolysosomal system. Loss or dysfunction of TRPMLs has been implicated in lysosomal storage disorders, infectious diseases, and metabolic diseases. TRPML2 has recently been identified as a mechanosensitive and hypotonicity-sensitive channel in endolysosomal organelles, which distinguishes it from TRPML1 and TRPML3. However, the molecular and gating mechanism of TRPML2 remains elusive. Here, we present the cryo-EM structure of the full-length mouse TRPML2 in lipid nanodiscs at 3.14 Å resolution. The TRPML2 homotetramer structure at pH 7.

SUBMITTER: Song X 

PROVIDER: S-EPMC8808176 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature