3HPK

Oxidized dimeric PICK1 PDZ in complex with the carboxyl tail peptide of GluR2

Summary for 3HPK

• Entry DOI: 10.2210/pdb3hpk/pdb
• Related: 2PKU 3HPM
• Descriptor: PRKCA-binding protein,9-mer peptide of THE GLUR2 SUBUNIT, GLYCEROL (3 entities in total)
• Functional Keywords: oxidized, pdz domain, kinase, protein binding
• Biological source: Rattus norvegicus (Rat); More
• Total number of polymer chains: 2
• Total formula weight: 26870.70

Authors

Yu, J.,Shi, Y.,Zhang, M. (deposition date: 2009-06-04, release date: 2010-06-09, Last modification date: 2024-10-30)

Primary citation

Shi, Y.,Yu, J.,Jia, Y.,Pan, L.,Shen, C.,Xia, J.,Zhang, M.
Redox-Regulated Lipid Membrane Binding of the PICK1 PDZ Domain.
Biochemistry, 49:4432-4439, 2010

PubMed 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.

PubMed: 20426484
DOI: 10.1021/bi100269t

Experimental method

X-RAY DIFFRACTION (2.2 Å)