6DMW
Calmodulin-bound full-length rbTRPV5
Summary for 6DMW
| Entry DOI | 10.2210/pdb6dmw/pdb |
| EMDB information | 7967 |
| Descriptor | Transient receptor potential cation channel subfamily V member 5, Calmodulin-1, CALCIUM ION (3 entities in total) |
| Functional Keywords | calmodulin, trpv5, full-length, calcium channel, transport protein |
| Biological source | Oryctolagus cuniculus (Rabbit) More |
| Total number of polymer chains | 5 |
| Total formula weight | 348571.40 |
| Authors | Hughes, T.E.T.,Pumroy, R.A.,Moiseenkova-Bell, V.Y. (deposition date: 2018-06-05, release date: 2018-10-24, Last modification date: 2024-03-13) |
| Primary citation | Hughes, T.E.T.,Pumroy, R.A.,Yazici, A.T.,Kasimova, M.A.,Fluck, E.C.,Huynh, K.W.,Samanta, A.,Molugu, S.K.,Zhou, Z.H.,Carnevale, V.,Rohacs, T.,Moiseenkova-Bell, V.Y. Structural insights on TRPV5 gating by endogenous modulators. Nat Commun, 9:4198-4198, 2018 Cited by PubMed Abstract: TRPV5 is a transient receptor potential channel involved in calcium reabsorption. Here we investigate the interaction of two endogenous modulators with TRPV5. Both phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) and calmodulin (CaM) have been shown to directly bind to TRPV5 and activate or inactivate the channel, respectively. Using cryo-electron microscopy (cryo-EM), we determined TRPV5 structures in the presence of dioctanoyl PI(4,5)P and CaM. The PI(4,5)P structure reveals a binding site between the N-linker, S4-S5 linker and S6 helix of TRPV5. These interactions with PI(4,5)P induce conformational rearrangements in the lower gate, opening the channel. The CaM structure reveals two TRPV5 C-terminal peptides anchoring a single CaM molecule and that calcium inhibition is mediated through a cation-π interaction between Lys116 on the C-lobe of calcium-activated CaM and Trp583 at the intracellular gate of TRPV5. Overall, this investigation provides insight into the endogenous modulation of TRPV5, which has the potential to guide drug discovery. PubMed: 30305626DOI: 10.1038/s41467-018-06753-6 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (4.4 Å) |
Structure validation
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