6E2F

Cryo-EM structure of human TRPV6 in complex with Calmodulin

Summary for 6E2F

• Entry DOI: 10.2210/pdb6e2f/pdb
• EMDB information: 8961
• Descriptor: Transient receptor potential cation channel subfamily V member 6, Calmodulin-1, CALCIUM ION (3 entities in total)
• Functional Keywords: trpv6, trp channels, calcium channels, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 350304.32

Authors

Singh, A.K.,McGoldrick, L.L.,Sobolevsky, A.I. (deposition date: 2018-07-11, release date: 2018-08-22, Last modification date: 2024-03-13)

Primary citation

Singh, A.K.,McGoldrick, L.L.,Twomey, E.C.,Sobolevsky, A.I.
Mechanism of calmodulin inactivation of the calcium-selective TRP channel TRPV6.
Sci Adv, 4:eaau6088-eaau6088, 2018

PubMed Abstract: Calcium (Ca) plays a major role in numerous physiological processes. Ca homeostasis is tightly controlled by ion channels, the aberrant regulation of which results in various diseases including cancers. Calmodulin (CaM)-mediated Ca-induced inactivation is an ion channel regulatory mechanism that protects cells against the toxic effects of Ca overload. We used cryo-electron microscopy to capture the epithelial calcium channel TRPV6 (transient receptor potential vanilloid subfamily member 6) inactivated by CaM. The TRPV6-CaM complex exhibits 1:1 stoichiometry; one TRPV6 tetramer binds both CaM lobes, which adopt a distinct head-to-tail arrangement. The CaM carboxyl-terminal lobe plugs the channel through a unique cation-π interaction by inserting the side chain of lysine K115 into a tetra-tryptophan cage at the pore's intracellular entrance. We propose a mechanism of CaM-mediated Ca-induced inactivation that can be explored for therapeutic design.

PubMed: 30116787
DOI: 10.1126/sciadv.aau6088

Experimental method

ELECTRON MICROSCOPY (3.9 Å)