2pku
From Proteopedia
(New page: 200px<br /><applet load="2pku" size="350" color="white" frame="true" align="right" spinBox="true" caption="2pku" /> '''Solution structure of PICK1 PDZ in complex w...) |
|||
| Line 4: | Line 4: | ||
==Overview== | ==Overview== | ||
| - | Protein interacting with c kinase 1 (PICK1) regulates the trafficking of | + | 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. |
==About this Structure== | ==About this Structure== | ||
| Line 22: | Line 22: | ||
[[Category: protein complex]] | [[Category: protein complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:30:38 2008'' |
Revision as of 16:30, 21 February 2008
|
Solution structure of PICK1 PDZ in complex with the carboxyl tail peptide of GluR2
Overview
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.
About this Structure
2PKU is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.
Reference
Clustering and synaptic targeting of PICK1 requires direct interaction between the PDZ domain and lipid membranes., Pan L, Wu H, Shen C, Shi Y, Jin W, Xia J, Zhang M, EMBO J. 2007 Oct 31;26(21):4576-87. Epub 2007 Oct 4. PMID:17914463
Page seeded by OCA on Thu Feb 21 18:30:38 2008
Categories: Rattus norvegicus | Single protein | Pan, L. | Shen, C. | Shi, Y. | Wu, H. | Xia, J. | Zhang, M. | Protein binding | Protein complex
