2lob

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{{STRUCTURE_2lob| PDB=2lob | SCENE= }}
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==PDZ Domain of CAL (Cystic Fibrosis Transmembrane Regulator-Associated Ligand)==
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===PDZ Domain of CAL (Cystic Fibrosis Transmembrane Regulator-Associated Ligand)===
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<StructureSection load='2lob' size='340' side='right' caption='[[2lob]], [[NMR_Ensembles_of_Models | 7 NMR models]]' scene=''>
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{{ABSTRACT_PUBMED_16331976}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[2lob]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LOB OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2LOB FirstGlance]. <br>
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</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GOPC, CAL, FIG ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<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>
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<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=2lob FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2lob OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2lob RCSB], [http://www.ebi.ac.uk/pdbsum/2lob PDBsum]</span></td></tr>
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</table>
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== Disease ==
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[[http://www.uniprot.org/uniprot/GOPC_HUMAN GOPC_HUMAN]] Note=A chromosomal aberration involving GOPC is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del(6)(q21q21) is responsible for the formation of GOPC-ROS1 chimeric protein which has a constitutive receptor tyrosine kinase activity.<ref>PMID:12661006</ref> [[http://www.uniprot.org/uniprot/CFTR_HUMAN CFTR_HUMAN]] Defects in CFTR are the cause of cystic fibrosis (CF) [MIM:[http://omim.org/entry/219700 219700]]; also known as mucoviscidosis. CF is the most common genetic disease in the Caucasian population, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive. CF is a common generalized disorder of exocrine gland function which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes.<ref>PMID:1695717</ref> <ref>PMID:2236053</ref> <ref>PMID:1710600</ref> <ref>PMID:1284466</ref> <ref>PMID:1284468</ref> <ref>PMID:1284530</ref> <ref>PMID:1284529</ref> <ref>PMID:7680525</ref> <ref>PMID:7683628</ref> <ref>PMID:7683954</ref> <ref>PMID:7505694</ref> <ref>PMID:7504969</ref> <ref>PMID:7522211</ref> <ref>PMID:7513296</ref> <ref>PMID:7525450</ref> <ref>PMID:7520022</ref> <ref>PMID:7524913</ref> <ref>PMID:7524909</ref> <ref>PMID:7517264</ref> <ref>PMID:8081395</ref> <ref>PMID:7544319</ref> <ref>PMID:8522333</ref> <ref>PMID:7537150</ref> <ref>PMID:7541273</ref> <ref>PMID:7581407</ref> <ref>PMID:7543567</ref> <ref>PMID:7541510</ref> <ref>PMID:8800923</ref> <ref>PMID:8829633</ref> <ref>PMID:8723693</ref> <ref>PMID:8723695</ref> <ref>PMID:8956039</ref> <ref>PMID:9101301</ref> <ref>PMID:9222768</ref> <ref>PMID:9375855</ref> <ref>PMID:9401006</ref> <ref>PMID:9443874</ref> <ref>PMID:9521595</ref> <ref>PMID:9921909</ref> <ref>PMID:9736778</ref> <ref>PMID:9482579</ref> <ref>PMID:9554753</ref> <ref>PMID:9452048</ref> <ref>PMID:9452054</ref> <ref>PMID:9452073</ref> <ref>PMID:10094564</ref> Defects in CFTR are the cause of congenital bilateral absence of the vas deferens (CBAVD) [MIM:[http://omim.org/entry/277180 277180]]. CBAVD is an important cause of sterility in men and could represent an incomplete form of cystic fibrosis, as the majority of men suffering from cystic fibrosis lack the vas deferens.<ref>PMID:7529962</ref> <ref>PMID:7539342</ref> <ref>PMID:9067761</ref> <ref>PMID:10651488</ref> [:]
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== Function ==
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[[http://www.uniprot.org/uniprot/GOPC_HUMAN GOPC_HUMAN]] Plays a role in intracellular protein trafficking and degradation. May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels. May also regulate the intracellular trafficking of the ADR1B receptor. May play a role in autophagy. Overexpression results in CFTR intracellular retention and degradation in the lysosomes.<ref>PMID:11707463</ref> <ref>PMID:14570915</ref> <ref>PMID:15358775</ref> [[http://www.uniprot.org/uniprot/CFTR_HUMAN CFTR_HUMAN]] Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1.<ref>PMID:22178883</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The association of the cystic fibrosis transmembrane regulator (CFTR) with two PDZ-containing molecular scaffolds (CAL and EBP50) plays an important role in CFTR trafficking and membrane maintenance. The CFTR-molecular scaffold interaction is mediated by the association of the C-terminus of the transmembrane regulator with the PDZ domains. Here, we characterize the structure and dynamics of the PDZ of CAL and the complex formed with CFTR employing high-resolution NMR. On the basis of NMR relaxation data, the alpha2 helix as well as the beta2-beta3 loop of CAL PDZ domain undergoes rapid dynamics. Molecular dynamics simulations suggest a concerted motion between the alpha2 helix and the beta1-beta2 and beta2-beta3 loops, elements which define the binding pocket, suggesting that dynamics may play a role in PDZ-ligand specificity. The C-terminus of CFTR binds to CAL with the final four residues (-D(-)(3)-T-R-L(0)) within the canonical PDZ-binding motif, between the beta2 strand and the alpha2 helix. The R(-)(1) and D(-)(3) side chains make a number of contacts with the PDZ domain; many of these interactions differ from those in the CFTR-EBP50 complex, suggesting sites that can be targeted in the development of PDZ-selective inhibitors that may help modulate CFTR function.
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==Disease==
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Association of the cystic fibrosis transmembrane regulator with CAL: structural features and molecular dynamics.,Piserchio A, Fellows A, Madden DR, Mierke DF Biochemistry. 2005 Dec 13;44(49):16158-66. PMID:16331976<ref>PMID:16331976</ref>
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[[http://www.uniprot.org/uniprot/GOPC_HUMAN GOPC_HUMAN]] Note=A chromosomal aberration involving GOPC is found in a glioblastoma multiforme sample. An intra-chromosomal deletion del(6)(q21q21) is responsible for the formation of GOPC-ROS1 chimeric protein which has a constitutive receptor tyrosine kinase activity.<ref>PMID:12661006</ref> [[http://www.uniprot.org/uniprot/CFTR_HUMAN CFTR_HUMAN]] Defects in CFTR are the cause of cystic fibrosis (CF) [MIM:[http://omim.org/entry/219700 219700]]; also known as mucoviscidosis. CF is the most common genetic disease in the Caucasian population, with a prevalence of about 1 in 2'000 live births. Inheritance is autosomal recessive. CF is a common generalized disorder of exocrine gland function which impairs clearance of secretions in a variety of organs. It is characterized by the triad of chronic bronchopulmonary disease (with recurrent respiratory infections), pancreatic insufficiency (which leads to malabsorption and growth retardation) and elevated sweat electrolytes.<ref>PMID:1695717</ref><ref>PMID:2236053</ref><ref>PMID:1710600</ref><ref>PMID:1284466</ref><ref>PMID:1284468</ref><ref>PMID:1284530</ref><ref>PMID:1284529</ref><ref>PMID:7680525</ref><ref>PMID:7683628</ref><ref>PMID:7683954</ref><ref>PMID:7505694</ref><ref>PMID:7504969</ref><ref>PMID:7522211</ref><ref>PMID:7513296</ref><ref>PMID:7525450</ref><ref>PMID:7520022</ref><ref>PMID:7524913</ref><ref>PMID:7524909</ref><ref>PMID:7517264</ref><ref>PMID:8081395</ref><ref>PMID:7544319</ref><ref>PMID:8522333</ref><ref>PMID:7537150</ref><ref>PMID:7541273</ref><ref>PMID:7581407</ref><ref>PMID:7543567</ref><ref>PMID:7541510</ref><ref>PMID:8800923</ref><ref>PMID:8829633</ref><ref>PMID:8723693</ref><ref>PMID:8723695</ref><ref>PMID:8956039</ref><ref>PMID:9101301</ref><ref>PMID:9222768</ref><ref>PMID:9375855</ref><ref>PMID:9401006</ref><ref>PMID:9443874</ref><ref>PMID:9521595</ref><ref>PMID:9921909</ref><ref>PMID:9736778</ref><ref>PMID:9482579</ref><ref>PMID:9554753</ref><ref>PMID:9452048</ref><ref>PMID:9452054</ref><ref>PMID:9452073</ref><ref>PMID:10094564</ref> Defects in CFTR are the cause of congenital bilateral absence of the vas deferens (CBAVD) [MIM:[http://omim.org/entry/277180 277180]]. CBAVD is an important cause of sterility in men and could represent an incomplete form of cystic fibrosis, as the majority of men suffering from cystic fibrosis lack the vas deferens.<ref>PMID:7529962</ref><ref>PMID:7539342</ref><ref>PMID:9067761</ref><ref>PMID:10651488</ref>[:]
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==Function==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[http://www.uniprot.org/uniprot/GOPC_HUMAN GOPC_HUMAN]] Plays a role in intracellular protein trafficking and degradation. May regulate CFTR chloride currents and acid-induced ASIC3 currents by modulating cell surface expression of both channels. May also regulate the intracellular trafficking of the ADR1B receptor. May play a role in autophagy. Overexpression results in CFTR intracellular retention and degradation in the lysosomes.<ref>PMID:11707463</ref><ref>PMID:14570915</ref><ref>PMID:15358775</ref> [[http://www.uniprot.org/uniprot/CFTR_HUMAN CFTR_HUMAN]] Involved in the transport of chloride ions. May regulate bicarbonate secretion and salvage in epithelial cells by regulating the SLC4A7 transporter. Can inhibit the chloride channel activity of ANO1.<ref>PMID:22178883</ref>
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</div>
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== References ==
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==About this Structure==
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<references/>
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[[2lob]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2LOB OCA].
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__TOC__
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</StructureSection>
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==Reference==
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<ref group="xtra">PMID:016331976</ref><references group="xtra"/><references/>
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[[Category: Channel-conductance-controlling ATPase]]
[[Category: Channel-conductance-controlling ATPase]]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Fellows, A.]]
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[[Category: Fellows, A]]
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[[Category: Madden, D R.]]
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[[Category: Madden, D R]]
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[[Category: Mierke, D F.]]
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[[Category: Mierke, D F]]
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[[Category: Piserchio, A.]]
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[[Category: Piserchio, A]]
[[Category: Peptide binding protein]]
[[Category: Peptide binding protein]]
[[Category: Structural protein-hydrolase complex]]
[[Category: Structural protein-hydrolase complex]]

Revision as of 16:48, 19 January 2015

PDZ Domain of CAL (Cystic Fibrosis Transmembrane Regulator-Associated Ligand)

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