6iv2: Difference between revisions
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==Crystal structure of a bacterial Bestrophin homolog from Klebsiella pneumoniae with a mutation Y211A== | |||
<StructureSection load='6iv2' size='340' side='right'caption='[[6iv2]], [[Resolution|resolution]] 2.62Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6iv2]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Klebsiella_pneumoniae_IS53 Klebsiella pneumoniae IS53]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6IV2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6IV2 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.62Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=6iv2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6iv2 OCA], [https://pdbe.org/6iv2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6iv2 RCSB], [https://www.ebi.ac.uk/pdbsum/6iv2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6iv2 ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Mutations of human BEST1, encoding a Ca(2+)-activated Cl(-) channel (hBest1), cause macular degenerative disorders. Best1 homolog structures reveal an evolutionarily conserved channel architecture highlighted by two landmark restrictions (named the "neck" and "aperture", respectively) in the ion conducting pathway, suggesting a unique dual-switch gating mechanism, which, however, has not been characterized well. Using patch clamp and crystallography, we demonstrate that both the neck and aperture in hBest1 are Ca(2+)-dependent gates essential for preventing channel leakage resulting from Ca(2+)-independent, spontaneous gate opening. Importantly, three patient-derived mutations (D203A, I205T and Y236C) lead to Ca(2+)-independent leakage and elevated Ca(2+)-dependent anion currents due to enhanced opening of the gates. Moreover, we identify a network of residues critically involved in gate operation. Together, our results suggest an indispensable role of the neck and aperture of hBest1 for channel gating, and uncover disease-causing mechanisms of hBest1 gain-of-function mutations. | |||
Dual Ca(2+)-dependent gates in human Bestrophin1 underlie disease-causing mechanisms of gain-of-function mutations.,Ji C, Kittredge A, Hopiavuori A, Ward N, Chen S, Fukuda Y, Zhang Y, Yang T Commun Biol. 2019 Jun 24;2:240. doi: 10.1038/s42003-019-0433-3. eCollection 2019. PMID:31263784<ref>PMID:31263784</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: Chen | <div class="pdbe-citations 6iv2" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Bestrophin 3D structures|Bestrophin 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Klebsiella pneumoniae IS53]] | |||
[[Category: Large Structures]] | |||
[[Category: Chen S]] | |||
[[Category: Kittredge A]] | |||
[[Category: Yang T]] | |||
Latest revision as of 22:26, 29 May 2024
Crystal structure of a bacterial Bestrophin homolog from Klebsiella pneumoniae with a mutation Y211ACrystal structure of a bacterial Bestrophin homolog from Klebsiella pneumoniae with a mutation Y211A
Structural highlights
Publication Abstract from PubMedMutations of human BEST1, encoding a Ca(2+)-activated Cl(-) channel (hBest1), cause macular degenerative disorders. Best1 homolog structures reveal an evolutionarily conserved channel architecture highlighted by two landmark restrictions (named the "neck" and "aperture", respectively) in the ion conducting pathway, suggesting a unique dual-switch gating mechanism, which, however, has not been characterized well. Using patch clamp and crystallography, we demonstrate that both the neck and aperture in hBest1 are Ca(2+)-dependent gates essential for preventing channel leakage resulting from Ca(2+)-independent, spontaneous gate opening. Importantly, three patient-derived mutations (D203A, I205T and Y236C) lead to Ca(2+)-independent leakage and elevated Ca(2+)-dependent anion currents due to enhanced opening of the gates. Moreover, we identify a network of residues critically involved in gate operation. Together, our results suggest an indispensable role of the neck and aperture of hBest1 for channel gating, and uncover disease-causing mechanisms of hBest1 gain-of-function mutations. Dual Ca(2+)-dependent gates in human Bestrophin1 underlie disease-causing mechanisms of gain-of-function mutations.,Ji C, Kittredge A, Hopiavuori A, Ward N, Chen S, Fukuda Y, Zhang Y, Yang T Commun Biol. 2019 Jun 24;2:240. doi: 10.1038/s42003-019-0433-3. eCollection 2019. PMID:31263784[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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