8fzq: Difference between revisions
From Proteopedia
Jump to navigationJump to search
m Protected "8fzq" [edit=sysop:move=sysop] |
No edit summary |
||
| Line 1: | Line 1: | ||
The | ==Dehosphorylated, ATP-bound human cystic fibrosis transmembrane conductance regulator (CFTR)== | ||
<StructureSection load='8fzq' size='340' side='right'caption='[[8fzq]], [[Resolution|resolution]] 4.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8fzq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8FZQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FZQ FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=8fzq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fzq OCA], [https://pdbe.org/8fzq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fzq RCSB], [https://www.ebi.ac.uk/pdbsum/8fzq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fzq ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel that regulates salt and fluid homeostasis across epithelial membranes(1). Alterations in CFTR cause cystic fibrosis, a fatal disease without a cure(2,3). Electrophysiological properties of CFTR have been analysed for decades(4-6). The structure of CFTR, determined in two globally distinct conformations, underscores its evolutionary relationship with other ATP-binding cassette transporters. However, direct correlations between the essential functions of CFTR and extant structures are lacking at present. Here we combine ensemble functional measurements, single-molecule fluorescence resonance energy transfer, electrophysiology and kinetic simulations to show that the two nucleotide-binding domains (NBDs) of human CFTR dimerize before channel opening. CFTR exhibits an allosteric gating mechanism in which conformational changes within the NBD-dimerized channel, governed by ATP hydrolysis, regulate chloride conductance. The potentiators ivacaftor and GLPG1837 enhance channel activity by increasing pore opening while NBDs are dimerized. Disease-causing substitutions proximal (G551D) or distal (L927P) to the ATPase site both reduce the efficiency of NBD dimerization. These findings collectively enable the framing of a gating mechanism that informs on the search for more efficacious clinical therapies. | |||
CFTR function, pathology and pharmacology at single-molecule resolution.,Levring J, Terry DS, Kilic Z, Fitzgerald G, Blanchard S, Chen J Nature. 2023 Mar 22. doi: 10.1038/s41586-023-05854-7. PMID:36949202<ref>PMID:36949202</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8fzq" style="background-color:#fffaf0;"></div> | ||
[[Category: Chen | == References == | ||
[[Category: | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: Terry | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | |||
[[Category: Blanchard SC]] | |||
[[Category: Chen J]] | |||
[[Category: Fitzgerald GA]] | |||
[[Category: Kilic Z]] | |||
[[Category: Levring J]] | |||
[[Category: Terry DS]] | |||
Revision as of 06:54, 29 March 2023
Dehosphorylated, ATP-bound human cystic fibrosis transmembrane conductance regulator (CFTR)
| ||||||||||||
