7aov | pdb_00007aov
Crystal Structure of a TRPM2 Domain
Structural highlights
Function[TRPM2_DANRE] Nonselective, voltage-independent cation channel that mediates Ca(2+) influx, leading to increased cytoplasmic Ca(2+) levels. Functions as ligand-gated ion channel. Binding of ADP-ribose to the cytoplasmic N-terminal region causes a conformation change; the channel is primed but still requires Ca(2+) binding to trigger channel opening.[1] Publication Abstract from PubMedTransient receptor potential melastatin 2 (TRPM2) is a Ca(2+) -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 Ca(2+) -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 Zn(2+) -binding domain that was not resolved in previous cryo-EM structures and that is conserved in most TRPM channels. In combination with patch clamp experiments we comprehensively characterize the effect of the Zn(2+) -binding domain on TRPM2 activation. Our results provide insight into a conserved motif essential for structural integrity and channel activity. The crystal structure of TRPM2 MHR1/2 domain reveals a conserved Zn(2+) -binding domain essential for structural integrity and channel activity.,Sander S, Pick J, Gattkowski E, Fliegert R, Tidow H Protein Sci. 2022 Jun;31(6):e4320. doi: 10.1002/pro.4320. PMID:35634784[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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