Novel CaM-binding motif in its NudT9H domain contributes to temperature sensitivity of TRPM2.

ABSTRACT: TRPM2 is a non-selective, Ca²⁺-permeable cation channel, which plays a role in cell death but also contributes to diverse immune cell functions. In addition, TRPM2 contributes to the control of body temperature and is involved in perception of non-noxious heat and thermotaxis. TRPM2 is regulated by many factors including Ca²⁺, ADPR, 2'-deoxy-ADPR, Ca²⁺-CaM, and temperature. However, the molecular basis for the temperature sensitivity of TRPM2 as well as the interplay between the regulatory factors is still not understood. Here we identify a novel CaM-binding site in the unique NudT9H domain of TRPM2. Using a multipronged biophysical approach we show that binding of Ca²⁺-CaM to this site occurs upon partial unfolding at temperatures >35 °C and pre

SUBMITTER: Gattkowski E 

PROVIDER: S-EPMC6646794 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature