2PKU: Solution structure of PICK1 PDZ in complex with the carboxyl tail peptide of GluR2

Citation:
Abstract
Protein interacting with c kinase 1 (PICK1) regulates the trafficking of receptors and ion-channels such as AMPA receptors. Traditionally, the PICK1 PDZ domain is regarded as an adaptor capable of binding to receptors trafficked by PICK1, and the lipid-binding BAR domain functions to tether PICK1 directly to membranes. Here, we show that the PICK1 PDZ domain can directly interact with lipid membranes. The PDZ domain and lipid membrane interaction is mediated by both a polybasic amino-acid cluster and a conserved 'Cys-Pro-Cys' motif located away from the peptide ligand-binding groove. Disruption of the PDZ and lipid membrane interaction totally abolished synaptic targeting of PICK1. Although mutation of the CPC motif did not affect the interaction between PICK1 and AMPA receptors, the mutant PICK1 was unable to cluster the GluR2 subunit of the receptor. In neurons, PICK1 containing the same mutation displayed dramatically compromised capacity in the trafficking of AMPA receptors. Taken together, our findings not only uncovered the novel lipid membrane-binding property of the PICK1 PDZ domain, but also provided direct evidence supporting the functional relevance of the PDZ-lipid interaction.
PDB ID: 2PKUDownload
MMDB ID: 60799
PDB Deposition Date: 2007/4/18
Updated in MMDB: 2007/11
Experimental Method:
solution nmr
Source Organism:
Rattus norvegicus
Similar Structures:
Molecular Components in 2PKU
Label Count Molecule
Proteins (2 molecules)
1
Prkca-binding Protein(Gene symbol: Pick1)
Molecule annotation
1
Peptide (Glu)(ser)(val)(lys)(ile)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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