Structure of a TRPM2 channel in complex with Ca²⁺ explains unique gating regulation.

ABSTRACT: Transient receptor potential melastatin 2 (TRPM2) is a Ca²⁺-permeable cation channel required for immune cell activation, insulin secretion, and body heat control. TRPM2 is activated by cytosolic Ca²⁺, phosphatidyl-inositol-4,5-bisphosphate and ADP ribose. Here, we present the ~3 Å resolution electron cryo-microscopic structure of TRPM2 from Nematostella vectensis, 63% similar in sequence to human TRPM2, in the Ca²⁺-bound closed state. Compared to other TRPM channels, TRPM2 exhibits unique structural features that correlate with its function. The pore is larger and more negatively charged, consistent with its high Ca²⁺ selectivity and larger conductance. The intracellular Ca²⁺ binding sites are connected to the pore and cytosol,

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC5976436 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature