5OEO

Solution structure of the complex of TRPV5(655-725) with a Calmodulin E32Q/E68Q double mutant

Summary for 5OEO

• Entry DOI: 10.2210/pdb5oeo/pdb
• NMR Information: BMRB: 34161
• Descriptor: Calmodulin-1, Transient receptor potential cation channel subfamily V member 5, CALCIUM ION (3 entities in total)
• Functional Keywords: trpv5, calcium channel, dynamics, calmodulin, regulation, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 24740.00

Authors

Vuister, G.W.,Bokhovchuk, F.M.,Bate, N.,Kovalevskaya, N.,Goult, B.T.,Spronk, C.A.E.M. (deposition date: 2017-07-09, release date: 2018-04-25, Last modification date: 2024-05-15)

Primary citation

Bokhovchuk, F.M.,Bate, N.,Kovalevskaya, N.V.,Goult, B.T.,Spronk, C.A.E.M.,Vuister, G.W.
The Structural Basis of Calcium-Dependent Inactivation of the Transient Receptor Potential Vanilloid 5 Channel.
Biochemistry, 57:2623-2635, 2018

PubMed Abstract: The transient receptor potential vanilloid channel subfamily member 5 (TRPV5) is a highly selective calcium ion channel predominately expressed in the kidney epithelium that plays an essential role in calcium reabsorption from renal infiltrate. In order to maintain Ca homeostasis, TRPV5 possesses a tightly regulated negative feedback mechanism, where the ubiquitous Ca binding protein calmodulin (CaM) directly binds to the intracellular TRPV5 C-terminus, thus regulating TRPV5. Here we report on the characterization of the TRPV5 C-terminal CaM binding site and its interaction with CaM at an atomistic level. We have solved the de novo solution structure of the TRPV5 C-terminus in complex with a CaM mutant, creating conditions that mimic the cellular basal Ca state. We demonstrate that under these conditions the TRPV5 C-terminus is exclusively bound to the CaM C-lobe only, while it confers conformational freedom to the CaM N-lobe. We also show that at elevated calcium levels, additional interactions between the TRPV5 C-terminus and CaM N-lobe occur, resulting in formation of a tight 1:1 complex, effectively making the N-lobe the calcium sensor. Together, these data are consistent with and support the novel model for Ca/CaM-dependent inactivation of TRPV channels as proposed by Bate and co-workers [ Bate , N. , et al. ( 2018 ) Biochemistry , ( 57), DOI: 10.1021/acs.biochem.7b01286 ].

PubMed: 29584409
DOI: 10.1021/acs.biochem.7b01287

Experimental method

SOLUTION NMR