Summary for 9M36
| Entry DOI | 10.2210/pdb9m36/pdb |
| EMDB information | 63600 |
| Descriptor | Short transient receptor potential channel 5, ZINC ION, PHOSPHATIDYLETHANOLAMINE, ... (6 entities in total) |
| Functional Keywords | ion channel, trpc5, calcium, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 366063.26 |
| Authors | Song, K.C.,Wei, M.,Chen, L. (deposition date: 2025-02-28, release date: 2025-07-02, Last modification date: 2025-11-12) |
| Primary citation | Chen, Y.,Song, K.,Guo, W.,Wei, M.,Chen, L. Mechanism of (-)-Englerin A and calcium binding on the human TRPC5 channel. Protein Sci., 34:e70218-e70218, 2025 Cited by PubMed Abstract: The natural product (-)-Englerin A (EA) selectively inhibits renal cancer cell growth by potently activating TRPC4 and TRPC5-containing ion channels. However, its binding site on these channels has remained elusive. In this study, we present two cryo-EM structures of human TRPC5 in complex with EA at 2.5 and 2.6 Å resolution, which reveal the EA-binding site and identify two major conformations influenced by calcium. EA binds between the pore helix and S5/S6 helices of hTRPC5, forming critical hydrophobic and polar interactions that underscore its specificity. Calcium binding at the intracellular domain of TRPC5 induces structural changes that stabilize the domain in a compact conformation. These findings expand our understanding of the structural pharmacology of TRPC5 and provide a framework for investigating calcium regulation in TRPC channels. PubMed: 40671342DOI: 10.1002/pro.70218 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.48 Å) |
Structure validation
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