3hpk
From Proteopedia
Oxidized dimeric PICK1 PDZ in complex with the carboxyl tail peptide of GluR2
Structural highlights
FunctionPICK1_RAT Probable adapter protein that bind to and organize the subcellular localization of a variety of membrane proteins containing some PDZ recognition sequence. Involved in the clustering of various receptors, possibly by acting at the receptor internalization level. Plays a role in synaptic plasticity by regulating the trafficking and internalization of AMPA receptors. May be regulated upon PRKCA activation. May regulate ASIC1/ASIC3 channel.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedPICK1 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. Redox-regulated lipid membrane binding of the PICK1 PDZ domain.,Shi Y, Yu J, Jia Y, Pan L, Shen C, Xia J, Zhang M Biochemistry. 2010 Jun 1;49(21):4432-9. PMID:20426484[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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