6d3r: Difference between revisions
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==Thermostablilized dephosphorylated chicken CFTR== | |||
<StructureSection load='6d3r' size='340' side='right' caption='[[6d3r]], [[Resolution|resolution]] 4.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6d3r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D3R FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Channel-conductance-controlling_ATPase Channel-conductance-controlling ATPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.3.49 3.6.3.49] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6d3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3r OCA], [http://pdbe.org/6d3r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3r RCSB], [http://www.ebi.ac.uk/pdbsum/6d3r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3r ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, crucial to epithelial salt and water homeostasis, and defective due to mutations in its gene in patients with cystic fibrosis, is a unique member of the large family of ATP-binding cassette transport proteins. Regulation of CFTR channel activity is stringently controlled by phosphorylation and nucleotide binding. Structural changes that underlie transitions between active and inactive functional states are not yet fully understood. Indeed the first 3D structures of dephosphorylated, ATP-free and phosphorylated ATP-bound states were only recently reported. Here we have determined the structure of inactive and active states of a thermally stabilized CFTR, the latter with very high channel open probability, confirmed after reconstitution into proteoliposomes. These structures, obtained at nominal resolution of 4.3 and 6.6 A, reveal a unique repositioning of the transmembrane helices and regulatory domain density that provide insights into the structural transition between active and inactive functional states of CFTR. Moreover, we observe an extracellular vestibule that may provide anion access to the pore due to the conformation of transmembrane helices 7 and 8 that differs from the previous orthologue CFTR structures. In conclusion, our work contributes detailed structural information on an active, open state of the CFTR anion channel. | |||
Cryo-EM visualization of an active high open probability CFTR anion channel.,Fay JF, Aleksandrov LA, Jensen T, Cui L, Kousouros JN, He L, Aleksandrov AA, Gingerich D, Riordan JR, Chen J Biochemistry. 2018 Oct 3. doi: 10.1021/acs.biochem.8b00763. PMID:30281975<ref>PMID:30281975</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6d3r" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Channel-conductance-controlling ATPase]] | |||
[[Category: Fay, J F]] | |||
[[Category: Riordan, J R]] | |||
[[Category: Cftr]] | |||
[[Category: Membrane protein]] | |||
Revision as of 10:56, 17 October 2018
Thermostablilized dephosphorylated chicken CFTRThermostablilized dephosphorylated chicken CFTR
Structural highlights
Publication Abstract from PubMedThe cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, crucial to epithelial salt and water homeostasis, and defective due to mutations in its gene in patients with cystic fibrosis, is a unique member of the large family of ATP-binding cassette transport proteins. Regulation of CFTR channel activity is stringently controlled by phosphorylation and nucleotide binding. Structural changes that underlie transitions between active and inactive functional states are not yet fully understood. Indeed the first 3D structures of dephosphorylated, ATP-free and phosphorylated ATP-bound states were only recently reported. Here we have determined the structure of inactive and active states of a thermally stabilized CFTR, the latter with very high channel open probability, confirmed after reconstitution into proteoliposomes. These structures, obtained at nominal resolution of 4.3 and 6.6 A, reveal a unique repositioning of the transmembrane helices and regulatory domain density that provide insights into the structural transition between active and inactive functional states of CFTR. Moreover, we observe an extracellular vestibule that may provide anion access to the pore due to the conformation of transmembrane helices 7 and 8 that differs from the previous orthologue CFTR structures. In conclusion, our work contributes detailed structural information on an active, open state of the CFTR anion channel. Cryo-EM visualization of an active high open probability CFTR anion channel.,Fay JF, Aleksandrov LA, Jensen T, Cui L, Kousouros JN, He L, Aleksandrov AA, Gingerich D, Riordan JR, Chen J Biochemistry. 2018 Oct 3. doi: 10.1021/acs.biochem.8b00763. PMID:30281975[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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