5t5n: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='5t5n' size='340' side='right'caption='[[5t5n]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='5t5n' size='340' side='right'caption='[[5t5n]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[5t5n]] is a 15 chain structure with sequence from [ | <table><tr><td colspan='2'>[[5t5n]] is a 15 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5T5N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5T5N FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1Å</td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5t5n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5t5n OCA], [https://pdbe.org/5t5n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5t5n RCSB], [https://www.ebi.ac.uk/pdbsum/5t5n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5t5n ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/E1C3A0_CHICK E1C3A0_CHICK] | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 19: | Line 22: | ||
==See Also== | ==See Also== | ||
*[[Antibody 3D structures|Antibody 3D structures]] | *[[Antibody 3D structures|Antibody 3D structures]] | ||
*[[Bestrophin 3D structures|Bestrophin 3D structures]] | |||
*[[3D structures of non-human antibody|3D structures of non-human antibody]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Gallus gallus]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Long | [[Category: Long SB]] | ||
[[Category: Vaisey | [[Category: Vaisey G]] | ||
Revision as of 15:54, 4 October 2023
Calcium-activated chloride channel bestrophin-1 (BEST1), triple mutant: I76A, F80A, F84A; in complex with an Fab antibody fragment, chloride, and calciumCalcium-activated chloride channel bestrophin-1 (BEST1), triple mutant: I76A, F80A, F84A; in complex with an Fab antibody fragment, chloride, and calcium
Structural highlights
FunctionPublication Abstract from PubMedCytoplasmic calcium (Ca2+) activates the bestrophin anion channel, allowing chloride ions to flow down their electrochemical gradient. Mutations in bestrophin 1 (BEST1) cause macular degenerative disorders. Previously, we determined an X-ray structure of chicken BEST1 that revealed the architecture of the channel. Here, we present electrophysiological studies of purified wild-type and mutant BEST1 channels and an X-ray structure of a Ca2+-independent mutant. From these experiments, we identify regions of BEST1 responsible for Ca2+ activation and ion selectivity. A "Ca2+ clasp" within the channel's intracellular region acts as a sensor of cytoplasmic Ca2+. Alanine substitutions within a hydrophobic "neck" of the pore, which widen it, cause the channel to be constitutively active, irrespective of Ca2+. We conclude that the primary function of the neck is as a "gate" that controls chloride permeation in a Ca2+-dependent manner. In contrast to what others have proposed, we find that the neck is not a major contributor to the channel's ion selectivity. We find that mutation of a cytosolic "aperture" of the pore does not perturb the Ca2+ dependence of the channel or its preference for anions over cations, but its mutation dramatically alters relative permeabilities among anions. The data suggest that the aperture functions as a size-selective filter that permits the passage of small entities such as partially dehydrated chloride ions while excluding larger molecules such as amino acids. Thus, unlike ion channels that have a single "selectivity filter," in bestrophin, distinct regions of the pore govern anion-vs.-cation selectivity and the relative permeabilities among anions. Distinct regions that control ion selectivity and calcium-dependent activation in the bestrophin ion channel.,Vaisey G, Miller AN, Long SB Proc Natl Acad Sci U S A. 2016 Nov 22;113(47):E7399-E7408. Epub 2016 Nov 7. PMID:27821745[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||