9M5V
Structure of human TRPC5 bound with (-)-englerin A,class1
This is a non-PDB format compatible entry.
Summary for 9M5V
| Entry DOI | 10.2210/pdb9m5v/pdb |
| EMDB information | 63651 |
| Descriptor | Short transient receptor potential channel 5, CHOLESTEROL HEMISUCCINATE, ZINC ION, ... (6 entities in total) |
| Functional Keywords | trpc5, ion channel, (-)-englerin a, cryo-em, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 454740.84 |
| Authors | Chen, Y.K.,Wei, M.,Chen, L.,Guo, W.J. (deposition date: 2025-03-06, 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 (2.53 Å) |
Structure validation
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