This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

4k6y

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Current revision

CFTR Associated Ligand (CAL) PDZ domain bound to peptide iCAL36-Q (ANSRWQTSII)

Structural highlights

4k6y is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.48Å
Ligands:
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

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4k6y"

Categories: Homo sapiens | Large Structures | Amacher JF | Madden DR

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[4k6y]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. 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 [https://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" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.48&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4k6y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k6y OCA], [https://pdbe.org/4k6y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4k6y RCSB], [https://www.ebi.ac.uk/pdbsum/4k6y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4k6y ProSAT]</span></td></tr>
 </table>

4k6y

From Proteopedia

Current revision

CFTR Associated Ligand (CAL) PDZ domain bound to peptide iCAL36-Q (ANSRWQTSII)

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox