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PDBsum entry 4jok
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Peptide binding protein
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PDB id
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4jok
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References listed in PDB file
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Key reference
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Title
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Stereochemical preferences modulate affinity and selectivity among five pdz domains that bind cftr: comparative structural and sequence analyses.
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Authors
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J.F.Amacher,
P.R.Cushing,
L.Brooks,
P.Boisguerin,
D.R.Madden.
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Ref.
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Structure, 2014,
22,
82-93.
[DOI no: ]
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PubMed id
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Abstract
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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.
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