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Mechanism of TRPM 2 channel gating revealed by cryo‐ EM
Author(s) -
Xia Shiyu,
Wang Longfei,
Fu TianMin,
Wu Hao
Publication year - 2019
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.14939
Subject(s) - transient receptor potential channel , microbiology and biotechnology , trpm2 , reactive oxygen species , intracellular , gating , chemistry , biophysics , biochemistry , receptor , biology
Transient receptor potential melastatin 2 ( TRPM 2) is a non‐selective cation channel that allows Ca 2+ influx across the plasma membrane and efflux from lysosomes upon opening. TRPM 2 is best known as a biosensor of reactive oxygen species ( ROS ), which mediates some of the body's responses to oxidative stress. As such, TRPM 2 is involved in a plethora of biological processes including immune response, insulin secretion, body temperature control and neuronal cell death, and represents an emerging therapeutic target for many human diseases, from diabetes to inflammatory and neurodegenerative diseases. A direct ligand of TRPM 2 is ADP ‐ribose ( ADPR ), which accumulates in cells at high levels of ROS , and activates TRPM 2 synergistically with intracellular calcium (Ca 2+ ). Here, we describe recent cryo‐electron microscopy (cryo‐ EM ) structures of TRPM 2 and summarize the insights they provided into the gating mechanism of the channel.