Human TRPML1 channel structures in open and closed conformations.

ABSTRACT: Transient receptor potential mucolipin 1 (TRPML1) is a Ca²⁺-releasing cation channel that mediates the calcium signalling and homeostasis of lysosomes. Mutations in TRPML1 lead to mucolipidosis type IV, a severe lysosomal storage disorder. Here we report two electron cryo-microscopy structures of full-length human TRPML1: a 3.72-Å apo structure at pH 7.0 in the closed state, and a 3.49-Å agonist-bound structure at pH 6.0 in an open state. Several aromatic and hydrophobic residues in pore helix 1, helices S5 and S6, and helix S6 of a neighbouring subunit, form a hydrophobic cavity to house the agonist, suggesting a distinct agonist-binding site from that found in TRPV1, a TRP channel from a different subfamily. The opening of TRPML1 is associated with distinct dilations of its lo

SUBMITTER: Schmiege P 

PROVIDER: S-EPMC5920536 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature