The crystal structure of TRPM2 MHR1/2 domain reveals a conserved Zn²⁺ -binding domain essential for structural integrity and channel activity.

ABSTRACT: Transient receptor potential melastatin 2 (TRPM2) is a Ca²⁺ -permeable, nonselective cation channel involved in diverse physiological processes such as immune response, apoptosis, and body temperature sensing. TRPM2 is activated by ADP-ribose (ADPR) and 2'-deoxy-ADPR in a Ca²⁺ -dependent manner. While two distinct binding sites exist for ADPR that exert different functions dependent on the species, the involvement of either binding site regarding the superagonistic effect of 2'-deoxy-ADPR is not clear yet. Here, we report the crystal structure of the MHR1/2 domain of TRPM2 from zebrafish (Danio rerio), and show that both ligands bind to this domain and activate the channel. We identified a so far unrecognized Zn²⁺ -binding domain that was not resolved in pr

SUBMITTER: Sander S 

PROVIDER: S-EPMC9112350 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature