4RDQ

Calcium-activated chloride channel bestrophin-1, from chicken, in complex with Fab antibody fragments, chloride and calcium

PDB DOI: https://doi.org/10.2210/pdb4RDQ/pdb

Classification: TRANSPORT PROTEIN
Organism(s): Gallus gallus, Mus musculus
Expression System: Komagataella pastoris
Mutation(s): No

Deposited: 2014-09-19 Released: 2014-10-22
Deposition Author(s): Dickson, V.K., Pedi, L., Long, S.B.

Experimental Data Snapshot

Method: X-RAY DIFFRACTION
Resolution: 2.85 Å
R-Value Free: 0.234
R-Value Work: 0.217
R-Value Observed: 0.218

wwPDB Validation 3D Report Full Report

Ligand Structure Quality Assessment

This is version 1.3 of the entry. See complete history.

Literature

Structure and insights into the function of a Ca(2+)-activated Cl(-) channel.

Kane Dickson, V., Pedi, L., Long, S.B.

(2014) Nature 516: 213-218

PubMed: 25337878 Search on PubMedSearch on PubMed Central
DOI: https://doi.org/10.1038/nature13913
Primary Citation of Related Structures:
4RDQ

PubMed Abstract:
Bestrophin calcium-activated chloride channels (CaCCs) regulate the flow of chloride and other monovalent anions across cellular membranes in response to intracellular calcium (Ca(2+)) levels. Mutations in bestrophin 1 (BEST1) cause certain eye diseases. Here we present X-ray structures of chicken BEST1-Fab complexes, at 2.85 Å resolution, with permeant anions and Ca(2+). Representing, to our knowledge, the first structure of a CaCC, the eukaryotic BEST1 channel, which recapitulates CaCC function in liposomes, is formed from a pentameric assembly of subunits. Ca(2+) binds to the channel's large cytosolic region. A single ion pore, approximately 95 Å in length, is located along the central axis and contains at least 15 binding sites for anions. A hydrophobic neck within the pore probably forms the gate. Phenylalanine residues within it may coordinate permeating anions via anion-π interactions. Conformational changes observed near the 'Ca(2+) clasp' hint at the mechanism of Ca(2+)-dependent gating. Disease-causing mutations are prevalent within the gating apparatus.

Organizational Affiliation

Structural Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, New York 10065, USA.

Macromolecule Content

Total Structure Weight: 479.36 kDa
Atom Count: 31,125
Modelled Residue Count: 3,945
Deposited Residue Count: 4,190
Unique protein chains: 3

Macromolecules

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Entity ID: 1
Molecule	Chains	Sequence Length	Organism	Details	Image
Bestrophin-1	A, B, C, D, E	409	Gallus gallus	Mutation(s): 0 Gene Names: Best1 bestrophin-1
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
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Reference Sequence

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Entity ID: 2
Molecule	Chains	Sequence Length	Organism	Details	Image
Fab antibody fragment, light chain	F, H, J, L, N	212	Mus musculus	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
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Reference Sequence

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Entity ID: 3
Molecule	Chains	Sequence Length	Organism	Details	Image
Fab antibody fragment, heavy chain	G, I, K, M, O	217	Mus musculus	Mutation(s): 0
Entity Groups
Sequence Clusters	30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
Sequence Annotations Expand
Reference Sequence

Small Molecules

Ligands 5 Unique
ID	Chains	Name / Formula / InChI Key	2D Diagram	3D Interactions
C6N Query on C6N Download Ideal Coordinates CCD File SDF format, chain CA [auth B] SDF format, chain KA [auth C] SDF format, chain QA [auth D] SDF format, chain V [auth A] SDF format, chain XA [auth E] MOL2 format, chain CA [auth B] MOL2 format, chain KA [auth C] MOL2 format, chain QA [auth D] MOL2 format, chain V [auth A] MOL2 format, chain XA [auth E]	CA [auth B], KA [auth C], QA [auth D], V [auth A], XA [auth E]	6-cyclohexyl-2-(4-cyclohexylbutyl)-2-({[4-O-(alpha-D-glucopyranosyl)-beta-D-glucopyranosyl]oxy}methyl)hexyl 4-O-alpha-D-glucopyranosyl-beta-D-glucopyranoside C₄₇ H₈₄ O₂₂ IBVSQWFQEONEKZ-VWHTXWAPSA-N		Interactions Focus chain CA [auth B] Focus chain KA [auth C] Focus chain QA [auth D] Focus chain V [auth A] Focus chain XA [auth E] Interactions & Density Focus chain CA [auth B] Focus chain KA [auth C] Focus chain QA [auth D] Focus chain V [auth A] Focus chain XA [auth E]
GOL Query on GOL Download Ideal Coordinates CCD File SDF format, chain DA [auth C] SDF format, chain LA [auth D] SDF format, chain P [auth A] SDF format, chain RA [auth E] SDF format, chain W [auth B] MOL2 format, chain DA [auth C] MOL2 format, chain LA [auth D] MOL2 format, chain P [auth A] MOL2 format, chain RA [auth E] MOL2 format, chain W [auth B]	DA [auth C], LA [auth D], P [auth A], RA [auth E], W [auth B]	GLYCEROL C₃ H₈ O₃ PEDCQBHIVMGVHV-UHFFFAOYSA-N		Interactions Focus chain DA [auth C] Focus chain LA [auth D] Focus chain P [auth A] Focus chain RA [auth E] Focus chain W [auth B] Interactions & Density Focus chain DA [auth C] Focus chain LA [auth D] Focus chain P [auth A] Focus chain RA [auth E] Focus chain W [auth B]
CA Query on CA Download Ideal Coordinates CCD File SDF format, chain EA [auth C] SDF format, chain MA [auth D] SDF format, chain S [auth A] SDF format, chain SA [auth E] SDF format, chain X [auth B] MOL2 format, chain EA [auth C] MOL2 format, chain MA [auth D] MOL2 format, chain S [auth A] MOL2 format, chain SA [auth E] MOL2 format, chain X [auth B]	EA [auth C], MA [auth D], S [auth A], SA [auth E], X [auth B]	CALCIUM ION Ca BHPQYMZQTOCNFJ-UHFFFAOYSA-N		Interactions Focus chain EA [auth C] Focus chain MA [auth D] Focus chain S [auth A] Focus chain SA [auth E] Focus chain X [auth B] Interactions & Density Focus chain EA [auth C] Focus chain MA [auth D] Focus chain S [auth A] Focus chain SA [auth E] Focus chain X [auth B]
K Query on K Download Ideal Coordinates CCD File SDF format, chain BA [auth B] SDF format, chain IA [auth C] SDF format, chain JA [auth C] SDF format, chain U [auth A] SDF format, chain WA [auth E] MOL2 format, chain BA [auth B] MOL2 format, chain IA [auth C] MOL2 format, chain JA [auth C] MOL2 format, chain U [auth A] MOL2 format, chain WA [auth E]	BA [auth B], IA [auth C], JA [auth C], U [auth A], WA [auth E]	POTASSIUM ION K NPYPAHLBTDXSSS-UHFFFAOYSA-N		Interactions Focus chain BA [auth B] Focus chain IA [auth C] Focus chain JA [auth C] Focus chain U [auth A] Focus chain WA [auth E] Interactions & Density Focus chain BA [auth B] Focus chain IA [auth C] Focus chain JA [auth C] Focus chain U [auth A] Focus chain WA [auth E]
CL Query on CL Download Ideal Coordinates CCD File SDF format, chain AA [auth B] SDF format, chain FA [auth C] SDF format, chain GA [auth C] SDF format, chain HA [auth C] SDF format, chain NA [auth D] SDF format, chain OA [auth D] SDF format, chain PA [auth D] SDF format, chain Q [auth A] SDF format, chain R [auth A] SDF format, chain T [auth A] SDF format, chain TA [auth E] SDF format, chain UA [auth E] SDF format, chain VA [auth E] SDF format, chain Y [auth B] SDF format, chain Z [auth B] MOL2 format, chain AA [auth B] MOL2 format, chain FA [auth C] MOL2 format, chain GA [auth C] MOL2 format, chain HA [auth C] MOL2 format, chain NA [auth D] MOL2 format, chain OA [auth D] MOL2 format, chain PA [auth D] MOL2 format, chain Q [auth A] MOL2 format, chain R [auth A] MOL2 format, chain T [auth A] MOL2 format, chain TA [auth E] MOL2 format, chain UA [auth E] MOL2 format, chain VA [auth E] MOL2 format, chain Y [auth B] MOL2 format, chain Z [auth B]	AA [auth B] FA [auth C] GA [auth C] HA [auth C] NA [auth D] AA [auth B], FA [auth C], GA [auth C], HA [auth C], NA [auth D], OA [auth D], PA [auth D], Q [auth A], R [auth A], T [auth A], TA [auth E], UA [auth E], VA [auth E], Y [auth B], Z [auth B]	CHLORIDE ION Cl VEXZGXHMUGYJMC-UHFFFAOYSA-M		Interactions Focus chain AA [auth B] Focus chain FA [auth C] Focus chain GA [auth C] Focus chain HA [auth C] Focus chain NA [auth D] Focus chain OA [auth D] Focus chain PA [auth D] Focus chain Q [auth A] Focus chain R [auth A] Focus chain T [auth A] Focus chain TA [auth E] Focus chain UA [auth E] Focus chain VA [auth E] Focus chain Y [auth B] Focus chain Z [auth B] Interactions & Density Focus chain AA [auth B] Focus chain FA [auth C] Focus chain GA [auth C] Focus chain HA [auth C] Focus chain NA [auth D] Focus chain OA [auth D] Focus chain PA [auth D] Focus chain Q [auth A] Focus chain R [auth A] Focus chain T [auth A] Focus chain TA [auth E] Focus chain UA [auth E] Focus chain VA [auth E] Focus chain Y [auth B] Focus chain Z [auth B]