4WD7

Crystal structure of a bacterial Bestrophin homolog from Klebsiella pneumoniae by Zn-SAD phasing

Summary for 4WD7

• Entry DOI: 10.2210/pdb4wd7/pdb
• Descriptor: Bestrophin domain protein, ZINC ION (2 entities in total)
• Functional Keywords: calcium-activated chloride channel, macular degeneration, single-wavelength anomalous diffraction (sad), sodium channel, pentamer, structural genomics, psi-biology, new york consortium on membrane protein structure, nycomps, membrane protein
• Biological source: Klebsiella pneumoniae UHKPC96
• Total number of polymer chains: 5
• Total formula weight: 172480.20

Authors

Yang, T.,Liu, Q.,Hendrickson, W.A.,New York Consortium on Membrane Protein Structure (NYCOMPS) (deposition date: 2014-09-08, release date: 2014-10-01, Last modification date: 2023-12-27)

Primary citation

Yang, T.,Liu, Q.,Kloss, B.,Bruni, R.,Kalathur, R.C.,Guo, Y.,Kloppmann, E.,Rost, B.,Colecraft, H.M.,Hendrickson, W.A.
Structure and selectivity in bestrophin ion channels.
Science, 346:355-359, 2014

PubMed Abstract: Human bestrophin-1 (hBest1) is a calcium-activated chloride channel from the retinal pigment epithelium, where mutations are associated with vitelliform macular degeneration, or Best disease. We describe the structure of a bacterial homolog (KpBest) of hBest1 and functional characterizations of both channels. KpBest is a pentamer that forms a five-helix transmembrane pore, closed by three rings of conserved hydrophobic residues, and has a cytoplasmic cavern with a restricted exit. From electrophysiological analysis of structure-inspired mutations in KpBest and hBest1, we find a sensitive control of ion selectivity in the bestrophins, including reversal of anion/cation selectivity, and dramatic activation by mutations at the cytoplasmic exit. A homology model of hBest1 shows the locations of disease-causing mutations and suggests possible roles in regulation.

PubMed: 25324390
DOI: 10.1126/science.1259723

Experimental method

X-RAY DIFFRACTION (2.9 Å)