6N27

BEST1 calcium-bound closed state

Summary for 6N27

• Entry DOI: 10.2210/pdb6n27/pdb
• Related: 6N23
• EMDB information: 9325
• Descriptor: Bestrophin homolog, CALCIUM ION (2 entities in total)
• Functional Keywords: ion channel, calcium activated chloride channel, eukaryotic membrane protein, anion channel, transport protein, ligand gated ion channel, membrane protein
• Biological source: Gallus gallus (Chicken)
• Total number of polymer chains: 5
• Total formula weight: 204009.03

Authors

Miller, A.N.,Vaisey, G.,Long, S.B. (deposition date: 2018-11-12, release date: 2019-01-23, Last modification date: 2019-12-18)

Primary citation

Miller, A.N.,Vaisey, G.,Long, S.B.
Molecular mechanisms of gating in the calcium-activated chloride channel bestrophin.
Elife, 8:-, 2019

PubMed Abstract: Bestrophin (BEST1-4) ligand-gated chloride (Cl) channels are activated by calcium (Ca). 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 Å 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 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.

PubMed: 30628889
DOI: 10.7554/eLife.43231

Experimental method

ELECTRON MICROSCOPY (3 Å)