7MBT
Cryo-EM structure of zebrafish TRPM5 E337A mutant in the presence of 5 mM calcium (low calcium occupancy in the transmembrane domain)
Summary for 7MBT
| Entry DOI | 10.2210/pdb7mbt/pdb |
| EMDB information | 23740 23741 23742 23743 23744 23745 23746 23747 23748 |
| Descriptor | Transient receptor potential melastatin 5, 2-acetamido-2-deoxy-beta-D-glucopyranose, (2R)-2-(hydroxymethyl)-4-{[(25R)-10alpha,14beta,17beta-spirost-5-en-3beta-yl]oxy}butyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside, ... (4 entities in total) |
| Functional Keywords | ion channel, trp channel, transport protein |
| Biological source | Danio rerio (Zebrafish, Brachydanio rerio) |
| Total number of polymer chains | 4 |
| Total formula weight | 536871.26 |
| Authors | |
| Primary citation | Ruan, Z.,Haley, E.,Orozco, I.J.,Sabat, M.,Myers, R.,Roth, R.,Du, J.,Lu, W. Structures of the TRPM5 channel elucidate mechanisms of activation and inhibition. Nat.Struct.Mol.Biol., 28:604-613, 2021 Cited by PubMed Abstract: The Ca-activated TRPM5 channel plays essential roles in taste perception and insulin secretion. However, the mechanism by which Ca regulates TRPM5 activity remains elusive. We report cryo-EM structures of the zebrafish TRPM5 in an apo closed state, a Ca-bound open state, and an antagonist-bound inhibited state. We define two novel ligand binding sites: a Ca site (Ca) in the intracellular domain and an antagonist site in the transmembrane domain (TMD). The Ca site is unique to TRPM5 and has two roles: modulating the voltage dependence and promoting Ca binding to the Ca site, which is conserved throughout TRPM channels. Conformational changes initialized from both Ca sites cooperatively open the ion-conducting pore. The antagonist NDNA wedges into the space between the S1-S4 domain and pore domain, stabilizing the transmembrane domain in an apo-like closed state. Our results lay the foundation for understanding the voltage-dependent TRPM channels and developing new therapeutic agents. PubMed: 34168372DOI: 10.1038/s41594-021-00607-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY |
Structure validation
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