8SR8
Cryo-EM structure of TRPM2 chanzyme in the presence of EDTA (apo state)
Summary for 8SR8
Entry DOI | 10.2210/pdb8sr8/pdb |
EMDB information | 40722 40895 |
Descriptor | TRPM2 chanzyme, CHOLESTEROL (2 entities in total) |
Functional Keywords | trpm2 chanzyme, channel-enzyme, transport protein |
Biological source | Salpingoeca rosetta |
Total number of polymer chains | 4 |
Total formula weight | 677649.78 |
Authors | |
Primary citation | Huang, Y.,Kumar, S.,Lee, J.,Lu, W.,Du, J. Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution. Nat.Struct.Mol.Biol., 31:1509-1521, 2024 Cited by PubMed Abstract: Channel enzymes represent a class of ion channels with enzymatic activity directly or indirectly linked to their channel function. We investigated a TRPM2 chanzyme from choanoflagellates that integrates two seemingly incompatible functions into a single peptide: a channel module activated by ADP-ribose with high open probability and an enzyme module (NUDT9-H domain) consuming ADP-ribose at a remarkably slow rate. Using time-resolved cryogenic-electron microscopy, we captured a complete series of structural snapshots of gating and catalytic cycles, revealing the coupling mechanism between channel gating and enzymatic activity. The slow kinetics of the NUDT9-H enzyme module confers a self-regulatory mechanism: ADPR binding triggers NUDT9-H tetramerization, promoting channel opening, while subsequent hydrolysis reduces local ADPR, inducing channel closure. We further demonstrated how the NUDT9-H domain has evolved from a structurally semi-independent ADP-ribose hydrolase module in early species to a fully integrated component of a gating ring essential for channel activation in advanced species. PubMed: 38773335DOI: 10.1038/s41594-024-01316-4 PDB entries with the same primary citation |
Experimental method | ELECTRON MICROSCOPY (2.77 Å) |
Structure validation
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