|
|
| Line 3: |
Line 3: |
| | <SX load='5uar' size='340' side='right' viewer='molstar' caption='[[5uar]], [[Resolution|resolution]] 3.73Å' scene=''> | | <SX load='5uar' size='340' side='right' viewer='molstar' caption='[[5uar]], [[Resolution|resolution]] 3.73Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5uar]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Brachidanio_rerio Brachidanio rerio]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5tsi 5tsi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UAR OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5UAR FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5uar]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=5tsi 5tsi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5UAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5UAR FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D10:DECANE'>D10</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]] 3.73Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5uak|5uak]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=D10:DECANE'>D10</scene></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=7955 Brachidanio rerio])</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=5uar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uar OCA], [https://pdbe.org/5uar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5uar RCSB], [https://www.ebi.ac.uk/pdbsum/5uar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5uar ProSAT]</span></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://proteopedia.org/fgij/fg.htm?mol=5uar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5uar OCA], [http://pdbe.org/5uar PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5uar RCSB], [http://www.ebi.ac.uk/pdbsum/5uar PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5uar ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/Q1LX78_DANRE Q1LX78_DANRE]] Involved in the transport of chloride ions.[RuleBase:RU362037] | + | [https://www.uniprot.org/uniprot/CFTR_DANRE CFTR_DANRE] Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:20933420, PubMed:23487313, PubMed:25592226). Mediates the transport of chloride ions across the cell membrane (By similarity). 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 (By similarity). Required for normal fluid homeostasis in the gut (PubMed:20933420). Required for normal volume expansion of Kupffer's vesicle during embryonic development and for normal establishment of left-right body patterning (PubMed:23487313, PubMed:26432887). Required for normal resistance to infection by P.aeruginosa strain PA14 and strain SMC573 (PubMed:20732993).[UniProtKB:P13569]<ref>PMID:20732993</ref> <ref>PMID:20933420</ref> <ref>PMID:23487313</ref> <ref>PMID:26432887</ref> <ref>PMID:25592226</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel evolved from the ATP-binding cassette (ABC) transporter family. In this study, we determined the structure of zebrafish CFTR in the absence of ATP by electron cryo-microscopy to 3.7 A resolution. Human and zebrafish CFTR share 55% sequence identity, and 42 of the 46 cystic-fibrosis-causing missense mutational sites are identical. In CFTR, we observe a large anion conduction pathway lined by numerous positively charged residues. A single gate near the extracellular surface closes the channel. The regulatory domain, dephosphorylated, is located in the intracellular opening between the two nucleotide-binding domains (NBDs), preventing NBD dimerization and channel opening. The structure also reveals why many cystic-fibrosis-causing mutations would lead to defects either in folding, ion conduction, or gating and suggests new avenues for therapeutic intervention.
| + | |
| - | | + | |
| - | Atomic Structure of the Cystic Fibrosis Transmembrane Conductance Regulator.,Zhang Z, Chen J Cell. 2016 Dec 1;167(6):1586-1597.e9. doi: 10.1016/j.cell.2016.11.014. PMID:27912062<ref>PMID:27912062</ref>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div> | + | |
| - | <div class="pdbe-citations 5uar" style="background-color:#fffaf0;"></div> | + | |
| | | | |
| | ==See Also== | | ==See Also== |
| Line 28: |
Line 17: |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Brachidanio rerio]] | + | [[Category: Danio rerio]] |
| - | [[Category: Channel-conductance-controlling ATPase]]
| + | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Chen, J]] | + | [[Category: Chen J]] |
| - | [[Category: Zhang, Z]] | + | [[Category: Zhang Z]] |
| - | [[Category: Abc transporter]]
| + | |
| - | [[Category: Anion channel]]
| + | |
| - | [[Category: Cystic fibrosis]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| Structural highlights
Function
CFTR_DANRE Epithelial ion channel that plays an important role in the regulation of epithelial ion and water transport and fluid homeostasis (PubMed:20933420, PubMed:23487313, PubMed:25592226). Mediates the transport of chloride ions across the cell membrane (By similarity). 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 (By similarity). Required for normal fluid homeostasis in the gut (PubMed:20933420). Required for normal volume expansion of Kupffer's vesicle during embryonic development and for normal establishment of left-right body patterning (PubMed:23487313, PubMed:26432887). Required for normal resistance to infection by P.aeruginosa strain PA14 and strain SMC573 (PubMed:20732993).[UniProtKB:P13569][1] [2] [3] [4] [5]
See Also
References
- ↑ Phennicie RT, Sullivan MJ, Singer JT, Yoder JA, Kim CH. Specific resistance to Pseudomonas aeruginosa infection in zebrafish is mediated by the cystic fibrosis transmembrane conductance regulator. Infect Immun. 2010 Nov;78(11):4542-50. doi: 10.1128/IAI.00302-10. Epub 2010 Aug, 23. PMID:20732993 doi:http://dx.doi.org/10.1128/IAI.00302-10
- ↑ Bagnat M, Navis A, Herbstreith S, Brand-Arzamendi K, Curado S, Gabriel S, Mostov K, Huisken J, Stainier DY. Cse1l is a negative regulator of CFTR-dependent fluid secretion. Curr Biol. 2010 Oct 26;20(20):1840-5. doi: 10.1016/j.cub.2010.09.012. Epub 2010, Oct 7. PMID:20933420 doi:http://dx.doi.org/10.1016/j.cub.2010.09.012
- ↑ Navis A, Marjoram L, Bagnat M. Cftr controls lumen expansion and function of Kupffer's vesicle in zebrafish. Development. 2013 Apr;140(8):1703-12. doi: 10.1242/dev.091819. Epub 2013 Mar 13. PMID:23487313 doi:http://dx.doi.org/10.1242/dev.091819
- ↑ Roxo-Rosa M, Jacinto R, Sampaio P, Lopes SS. The zebrafish Kupffer's vesicle as a model system for the molecular mechanisms by which the lack of Polycystin-2 leads to stimulation of CFTR. Biol Open. 2015 Oct 2;4(11):1356-66. doi: 10.1242/bio.014076. PMID:26432887 doi:http://dx.doi.org/10.1242/bio.014076
- ↑ Navis A, Bagnat M. Loss of cftr function leads to pancreatic destruction in larval zebrafish. Dev Biol. 2015 Mar 15;399(2):237-48. doi: 10.1016/j.ydbio.2014.12.034. Epub 2015 , Jan 13. PMID:25592226 doi:http://dx.doi.org/10.1016/j.ydbio.2014.12.034
|
