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| | <SX load='6d3s' size='340' side='right' viewer='molstar' caption='[[6d3s]], [[Resolution|resolution]] 6.60Å' scene=''> | | <SX load='6d3s' size='340' side='right' viewer='molstar' caption='[[6d3s]], [[Resolution|resolution]] 6.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6d3s]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Chick Chick]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3S OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6D3S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6d3s]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Gallus_gallus Gallus gallus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D3S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D3S 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></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 6.6Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CFTR ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9031 CHICK])</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></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'>[https://proteopedia.org/fgij/fg.htm?mol=6d3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3s OCA], [https://pdbe.org/6d3s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d3s RCSB], [https://www.ebi.ac.uk/pdbsum/6d3s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3s ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6d3s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d3s OCA], [http://pdbe.org/6d3s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d3s RCSB], [http://www.ebi.ac.uk/pdbsum/6d3s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d3s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/A0M8U4_CHICK A0M8U4_CHICK]] Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis. Mediates the transport of chloride ions across the cell membrane. Channel activity is coupled to ATP hydrolysis. The ion channel is also permeable to HCO(3-); selectivity depends on the extracellular chloride concentration. Exerts its function also by modulating the activity of other ion channels and transporters. Contributes to the regulation of the pH and the ion content of the epithelial fluid layer.[RuleBase:RU362037] | + | [https://www.uniprot.org/uniprot/A0A1D5PBN0_CHICK A0A1D5PBN0_CHICK] |
| - | <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.
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| - | | + | |
| - | 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>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6d3s" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| | *[[ABC transporter 3D structures|ABC transporter 3D structures]] | | *[[ABC transporter 3D structures|ABC transporter 3D structures]] |
| - | == References == | |
| - | <references/> | |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Channel-conductance-controlling ATPase]] | + | [[Category: Gallus gallus]] |
| - | [[Category: Chick]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, Z J]] | + | [[Category: Chen ZJ]] |
| - | [[Category: Fay, J F]] | + | [[Category: Fay JF]] |
| - | [[Category: Riordan, J R]] | + | [[Category: Riordan JR]] |
| - | [[Category: Cftr]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
