4jor
From Proteopedia
CFTR Associated Ligand (CAL) PDZ domain bound to HPV18 E6 oncoprotein C-terminal peptide (RLQRRRETQV)
Structural highlights
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] [VE6_HPV18] Transcriptional transactivator. Binds double stranded DNA (By similarity). Has transforming activity. Inactivates, with E6-AP ubiquitin-protein ligase, the human p53/TP53 tumor suppressor protein by targeting it to degradation. Binds and targets human MUPP1/MPDZ protein to degradation. Those two functions presumably contribute to transforming activity. Interaction with human FBLN1 protein also seems to be linked to cell transformation. Publication Abstract from PubMedPDZ 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
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