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-Structure paper
タイトル | Coupling enzymatic activity and gating in an ancient TRPM chanzyme and its molecular evolution. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 31, Issue 10, Page 1509-1521, Year 2024 |
掲載日 | 2024年5月21日 |
著者 | Yihe Huang / Sushant Kumar / Junuk Lee / Wei Lü / Juan Du / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Struct Mol Biol / PubMed:38773335 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 1.97 - 4.14 Å |
構造データ | EMDB-40721, PDB-8sr7: EMDB-40722, PDB-8sr8: EMDB-40723, PDB-8sr9: EMDB-40724, PDB-8sra: EMDB-40725, PDB-8srb: EMDB-40726, PDB-8src: EMDB-40727, PDB-8srd: EMDB-40728, PDB-8sre: EMDB-40729, PDB-8srf: EMDB-40730, PDB-8srg: EMDB-40731, PDB-8srh: EMDB-40732, PDB-8sri: EMDB-40733, PDB-8srj: EMDB-40734, PDB-8srk: EMDB-40865: NUDT9-H domain focused cryo-EM map of TRPM2 chanzyme in the presence of Calcium and ADP-ribose EMDB-40866: NUDT9-H domain focused cryo-EM map of TRPM2 chanzyme in the presence of Magnesium, Adenosine monophosphate, and Ribose-5-phosphate EMDB-40867: NUDT9-H domain focused cryo-EM map of TRPM2 chanzyme in the presence of Magnesium, Adenosine monophosphate, and Ribose-5-phosphate EMDB-40868: NUDT9-H domain focused cryo-EM map of TRPM2 chanzyme in the presence of Magnesium and ADP-ribose, open state EMDB-40869: NUDT9-H domain focused cryo-EM map of TRPM2 chanzyme in the presence of Magnesium and ADP-ribose, closed state EMDB-40870: NUDT9-H domain focused cryo-EM map of TRPM2 chanzyme in the presence of Magnesium, ADP-ribose, Adenosine monophosphate, and Ribose-5-phosphate, closed state EMDB-40871: NUDT9-H domain focused cryo-EM map of TRPM2 chanzyme (E1114A) in the presence of Magnesium and ADP-ribose, open state EMDB-40872: NUDT9-H domain focused cryo-EM map of TRPM2 chanzyme (E1114A) in the presence of Magnesium and ADP-ribose, closed state EMDB-40875: Raw consensus map of TRPM2 chanzyme in the presence of Magnesium, Adenosine monophosphate, and Ribose-5-phosphate EMDB-40876: Raw consensus map of TRPM2 chanzyme in the presence of Magnesium EMDB-40877: Raw consensus map of TRPM2 chanzyme in the presence of Calcium EMDB-40878: Raw consensus map of TRPM2 chanzyme in the presence of EDTA and ADP-ribose EMDB-40879: Raw consensus map of TRPM2 chanzyme in the presence of Magnesium and ADP-ribose, open state EMDB-40880: Raw consensus map of TRPM2 chanzyme in the presence of Magnesium and ADP-ribose, closed state EMDB-40881: Raw consensus map of TRPM2 chanzyme in the presence of Magnesium, ADP-ribose, Adenosine monophosphate, and Ribose-5-phosphate, closed state EMDB-40883: Raw consensus map of TRPM2 chanzyme in the presence of Magnesium, Adenosine monophosphate, and Ribose-5-phosphate EMDB-40887: Raw consensus map of TRPM2 chanzyme (E1114A) in the presence of Magnesium and ADP-ribose, open state EMDB-40888: Raw consensus map of TRPM2 chanzyme (E1114A) in the presence of Magnesium and ADP-ribose, closed state EMDB-40893: Raw consensus map of TRPM2 chanzyme in the presence of Calcium and ADP-ribose. EMDB-40895: Raw consensus map of TRPM2 chanzyme in the presence of EDTA (apo state) |
化合物 | ChemComp-RP5: ChemComp-AMP: ChemComp-MG: ChemComp-CLR: ChemComp-HOH: ChemComp-CA: ChemComp-APR: |
由来 |
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キーワード | TRANSPORT PROTEIN / TRPM2 Chanzyme / Channel-enzyme / MEMBRANE PROTEIN |