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| | ==CFTR Associated Ligand (CAL) PDZ domain bound to peptide iCAL36-Q (ANSRWQTSII)== | | ==CFTR Associated Ligand (CAL) PDZ domain bound to peptide iCAL36-Q (ANSRWQTSII)== |
| - | <StructureSection load='4k6y' size='340' side='right' caption='[[4k6y]], [[Resolution|resolution]] 1.48Å' scene=''> | + | <StructureSection load='4k6y' size='340' side='right'caption='[[4k6y]], [[Resolution|resolution]] 1.48Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4k6y]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K6Y OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K6Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4k6y]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K6Y OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=4K6Y FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr> |
| | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k72|4k72]], [[4k75|4k75]], [[4k76|4k76]], [[4k78|4k78]], [[4joe|4joe]], [[4jof|4jof]], [[4jog|4jog]], [[4joh|4joh]], [[4joj|4joj]], [[4jok|4jok]]</td></tr> | | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k72|4k72]], [[4k75|4k75]], [[4k76|4k76]], [[4k78|4k78]], [[4joe|4joe]], [[4jof|4jof]], [[4jog|4jog]], [[4joh|4joh]], [[4joj|4joj]], [[4jok|4jok]]</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 HUMAN])</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 HUMAN])</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=4k6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k6y OCA], [http://pdbe.org/4k6y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k6y RCSB], [http://www.ebi.ac.uk/pdbsum/4k6y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k6y 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=4k6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k6y OCA], [http://pdbe.org/4k6y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4k6y RCSB], [http://www.ebi.ac.uk/pdbsum/4k6y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4k6y ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Amacher, J F]] | | [[Category: Amacher, J F]] |
| | [[Category: Madden, D R]] | | [[Category: Madden, D R]] |
| Structural highlights
4k6y is a 4 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | |
| Related: | 4k72, 4k75, 4k76, 4k78, 4joe, 4jof, 4jog, 4joh, 4joj, 4jok |
| Gene: | GOPC, CAL, FIG (HUMAN) |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Disease
[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.[1]
Function
[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.[2] [3] [4]
Publication Abstract from PubMed
PDZ domain interactions are involved in signaling and trafficking pathways that coordinate crucial cellular processes. Alignment-based PDZ binding motifs identify the few most favorable residues at certain positions along the peptide backbone. However, sequences that bind the CAL (CFTR-associated ligand) PDZ domain reveal only a degenerate motif that overpredicts the true number of high-affinity interactors. Here, we combine extended peptide-array motif analysis with biochemical techniques to show that non-motif "modulator" residues influence CAL binding. The crystallographic structures of 13 CAL:peptide complexes reveal defined, but accommodating stereochemical environments at non-motif positions, which are reflected in modulator preferences uncovered by multisequence substitutional arrays. These preferences facilitate the identification of high-affinity CAL binding sequences and differentially affect CAL and NHERF PDZ binding. As a result, they also help determine the specificity of a PDZ domain network that regulates the trafficking of CFTR at the apical membrane.
Stereochemical Preferences Modulate Affinity and Selectivity among Five PDZ Domains that Bind CFTR: Comparative Structural and Sequence Analyses.,Amacher JF, Cushing PR, Brooks L 3rd, Boisguerin P, Madden DR Structure. 2014 Jan 7;22(1):82-93. doi: 10.1016/j.str.2013.09.019. Epub 2013 Nov , 7. PMID:24210758[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Charest A, Lane K, McMahon K, Park J, Preisinger E, Conroy H, Housman D. Fusion of FIG to the receptor tyrosine kinase ROS in a glioblastoma with an interstitial del(6)(q21q21). Genes Chromosomes Cancer. 2003 May;37(1):58-71. PMID:12661006 doi:10.1002/gcc.10207
- ↑ Cheng J, Moyer BD, Milewski M, Loffing J, Ikeda M, Mickle JE, Cutting GR, Li M, Stanton BA, Guggino WB. A Golgi-associated PDZ domain protein modulates cystic fibrosis transmembrane regulator plasma membrane expression. J Biol Chem. 2002 Feb 1;277(5):3520-9. Epub 2001 Nov 13. PMID:11707463 doi:10.1074/jbc.M110177200
- ↑ Cheng J, Wang H, Guggino WB. Modulation of mature cystic fibrosis transmembrane regulator protein by the PDZ domain protein CAL. J Biol Chem. 2004 Jan 16;279(3):1892-8. Epub 2003 Oct 21. PMID:14570915 doi:10.1074/jbc.M308640200
- ↑ He J, Bellini M, Xu J, Castleberry AM, Hall RA. Interaction with cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) inhibits beta1-adrenergic receptor surface expression. J Biol Chem. 2004 Nov 26;279(48):50190-6. Epub 2004 Sep 9. PMID:15358775 doi:10.1074/jbc.M404876200
- ↑ Amacher JF, Cushing PR, Brooks L 3rd, Boisguerin P, Madden DR. Stereochemical Preferences Modulate Affinity and Selectivity among Five PDZ Domains that Bind CFTR: Comparative Structural and Sequence Analyses. Structure. 2014 Jan 7;22(1):82-93. doi: 10.1016/j.str.2013.09.019. Epub 2013 Nov , 7. PMID:24210758 doi:http://dx.doi.org/10.1016/j.str.2013.09.019
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