PDBsum entry 4k76

Peptide binding protein/protein binding

PDB id: 4k76

Contents

Protein chains

87 a.a.

Ligands

SER-ARG-TRP-PRO-THR-THR-ARG-LEU

ASN-SER-ARG-TRP-PRO-THR-THR-ARG-LEU

ARG-TRP-PRO-THR-THR-ARG-LEU

TRP-PRO-THR-THR-ARG-LEU

GOL

Waters ×267

PDB id:

4k76

Name:

Peptide binding protein/protein binding

Title:

Cftr associated ligand (cal) pdz domain bound to peptide ical36-trl (ansrwpttrl)

Structure:

Golgi-associated pdz and coiled-coil motif-containing protein. Chain: a, b, c, d. Fragment: pdz domain. Synonym: cftr-associated ligand, fused in glioblastoma, pdz protein interacting specifically with tc10, pist. Engineered: yes. Ical36-trl peptide. Chain: e, f, g, h.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: gopc, cal, fig. Expressed in: escherichia coli. Expression_system_taxid: 469008. Synthetic: yes

Resolution:

1.75Å R-factor: 0.175 R-free: 0.221

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

Date:

16-Apr-13 Release date: 26-Feb-14

Protein chains

Q9HD26  (GOPC_HUMAN) -  Golgi-associated PDZ and coiled-coil motif-containing protein from Homo sapiens

Seq: 462 a.a.

Struc: 87 a.a.

DOI no: 10.1016/j.str.2013.09.019

Structure 22:82-93 (2014)

PubMed id: 24210758

Stereochemical preferences modulate affinity and selectivity among five PDZ domains that bind CFTR: comparative structural and sequence analyses.

J.F.Amacher, P.R.Cushing, L.Brooks, P.Boisguerin, D.R.Madden.

ABSTRACT

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.