7B5C

Structure of calcium-bound mTMEM16A(ac) chloride channel at 3.7 A resolution

Summary for 7B5C

• Entry DOI: 10.2210/pdb7b5c/pdb
• EMDB information: 12025
• Descriptor: Anoctamin-1, CALCIUM ION (2 entities in total)
• Functional Keywords: ligand-gated ion channel, anoctamin-1, membrane protein
• Biological source: Mus musculus (Mouse)
• Total number of polymer chains: 2
• Total formula weight: 222278.30

Authors

Lam, A.K.M.,Rheinberger, J.,Paulino, C.,Dutzler, R. (deposition date: 2020-12-03, release date: 2021-02-10, Last modification date: 2024-10-16)

Primary citation

Lam, A.K.M.,Rheinberger, J.,Paulino, C.,Dutzler, R.
Gating the pore of the calcium-activated chloride channel TMEM16A.
Nat Commun, 12:785-785, 2021

PubMed Abstract: The binding of cytoplasmic Ca to the anion-selective channel TMEM16A triggers a conformational change around its binding site that is coupled to the release of a gate at the constricted neck of an hourglass-shaped pore. By combining mutagenesis, electrophysiology, and cryo-electron microscopy, we identified three hydrophobic residues at the intracellular entrance of the neck as constituents of this gate. Mutation of each of these residues increases the potency of Ca and results in pronounced basal activity. The structure of an activating mutant shows a conformational change of an α-helix that contributes to Ca binding as a likely cause for the basal activity. Although not in physical contact, the three residues are functionally coupled to collectively contribute to the stabilization of the gate in the closed conformation of the pore, thus explaining the low open probability of the channel in the absence of Ca.

PubMed: 33542223
DOI: 10.1038/s41467-020-20787-9

Experimental method

ELECTRON MICROSCOPY (3.7 Å)