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8SR8

Cryo-EM structure of TRPM2 chanzyme in the presence of EDTA (apo state)

Summary for 8SR8
Entry DOI10.2210/pdb8sr8/pdb
EMDB information40722 40895
DescriptorTRPM2 chanzyme, CHOLESTEROL (2 entities in total)
Functional Keywordstrpm2 chanzyme, channel-enzyme, transport protein
Biological sourceSalpingoeca rosetta
Total number of polymer chains4
Total formula weight677649.78
Authors
Huang, Y.,Kumar, S.,Lu, W.,Du, J. (deposition date: 2023-05-05, release date: 2024-05-08, Last modification date: 2024-10-30)
Primary citationHuang, 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: 38773335
DOI: 10.1038/s41594-024-01316-4
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (2.77 Å)
Structure validation

227111

數據於2024-11-06公開中

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