Golgi-associated pdz and coiled-coil motif-containing protein. Chain: a, b. Fragment: cal pdz domain. Engineered: yes. Protein e6. Chain: c, d. Fragment: hpv16 e6 peptide. Engineered: yes
Source:
Homo sapiens. Human. Organism_taxid: 9606. Gene: gopc, cal, fig. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes. Human papillomavirus type 16. Organism_taxid: 333760
Resolution:
1.80Å
R-factor:
0.181
R-free:
0.219
Authors:
J.F.Amacher,D.R.Madden
Key ref:
J.F.Amacher
et al.
(2014).
Stereochemical preferences modulate affinity and selectivity among five PDZ domains that bind CFTR: comparative structural and sequence analyses.
Structure,
22,
82-93.
PubMed id: 24210758
DOI: 10.1016/j.str.2013.09.019
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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