8srj

Cryo-EM structure of TRPM2 chanzyme (without NUDT9-H domain) in the presence of EDTA, apo state

spinqualitylabelsall models 8srj, resolution 3.74Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8srj is a 4 chain structure with sequence from Salpingoeca rosetta. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.74Å Ligands: CLR Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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. Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution.,Huang Y, Kumar S, Lee J, Lu W, Du J Nat Struct Mol Biol. 2024 May 21. doi: 10.1038/s41594-024-01316-4. PMID:38773335 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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