PDBsum entry 3hpm

Protein binding

PDB id: 3hpm

Contents

Protein chains

108 a.a. *

Waters ×1

* Residue conservation analysis

PDB id:

3hpm

Name:

Protein binding

Title:

Oxidized dimeric pick1 pdz c46g mutant in complex with the carboxyl tail peptide of glur2

Structure:

Prkca-binding protein,9-mer peptide of the glur2 subunit. Chain: a, b. Fragment: pick1 pdz domain. Synonym: protein interacting with c kinase 1,isoform cra_b,protein interacting with prkca 1. Engineered: yes. Mutation: yes

Source:

Rattus norvegicus, synthetic construct. Rat. Organism_taxid: 10116, 32630. Gene: pick1, rcg_60080. Expressed in: escherichia coli. Expression_system_taxid: 469008.

Resolution:

2.80Å R-factor: 0.248 R-free: 0.295

Authors:

J.Yu,Y.Shi,M.Zhang

Key ref:

Y.Shi et al. (2010). Redox-regulated lipid membrane binding of the PICK1 PDZ domain. Biochemistry, 49, 4432-4439. PubMed id: 20426484

Date:

04-Jun-09 Release date: 09-Jun-10

Protein chains

Q9EP80  (PICK1_RAT) -  PRKCA-binding protein from Rattus norvegicus

Seq: 416 a.a.

Struc: 108 a.a.*

* PDB and UniProt seqs differ at 16 residue positions (black crosses)

Biochemistry 49:4432-4439 (2010)

PubMed id: 20426484

Redox-regulated lipid membrane binding of the PICK1 PDZ domain.

Y.Shi, J.Yu, Y.Jia, L.Pan, C.Shen, J.Xia, M.Zhang.

ABSTRACT

PICK1 is a PDZ/BAR domain-containing scaffold protein that regulates the trafficking of many receptors and ion channels, including AMPA receptors. In addition to binding to a wide spectrum of target proteins to be transported, the PICK1 PDZ domain, via its conserved CPC motif, has also been shown to bind to lipid membranes. However, the molecular basis of the CPC motif-mediated lipid membrane binding of the PICK1 PDZ domain is not known. Here we show that the Cys residues in the CPC motif of the PICK1 PDZ domain forms reversible, intermolecular disulfide bonds under mild oxidation conditions. Importantly, formation of the disulfide-mediated dimer abolishes the lipid membrane binding capacity of the PICK1 PDZ domain and thereby is expected to alter the cellular functions of PICK1. The structures of the PDZ dimers provide atomic-scale pictures of disulfide-mediated PICK1 dimer formation and a molecular explanation of the oxidation-induced dissociation of PICK1 from membranes. We propose that the PICK1-mediated trafficking processes might be regulated by cellular redox fluctuations under both physiological and pathophysiological conditions.