6n27

BEST1 calcium-bound closed state

Loading... Status: waiting for Mol* initialization Structural highlights 6n27 is a 5 chain structure with sequence from Chick. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CA Related: 6n23 Gene: BEST1 (CHICK) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Bestrophin (BEST1-4) ligand-gated chloride (Cl(-)) channels are activated by calcium (Ca(2+)). Mutation of BEST1 causes retinal disease. Partly because bestrophin channels have no sequence or structural similarity to other ion channels, the molecular mechanisms underlying gating are unknown. Here, we present a series of cryo-electron microscopy structures of chicken BEST1, determined at 3.1 A resolution or better, that represent the channel's principal gating states. Unlike other channels, opening of the pore is due to the repositioning of tethered pore-lining helices within a surrounding protein shell that dramatically widens a neck of the pore through a concertina of amino acid rearrangements. The neck serves as both the activation and the inactivation gate. Ca(2+) binding instigates opening of the neck through allosteric means whereas inactivation peptide binding induces closing. An aperture within the otherwise wide pore controls anion permeability. The studies define a new molecular paradigm for gating among ligand-gated ion channels. Molecular mechanisms of gating in the calcium-activated chloride channel bestrophin.,Miller AN, Vaisey G, Long SB Elife. 2019 Jan 10;8. pii: 43231. doi: 10.7554/eLife.43231. PMID:30628889 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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