Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Sci. STKE, 22 April 2003
Vol. 2003, Issue 179, p. re7
[DOI: 10.1126/scisignal.1792003re7]

REVIEWS

PDZ Domain Proteins: Plug and Play!

Claire Nourry1, Seth G. N. Grant2, and Jean-Paul Borg1*

1U119 INSERM and Institut Paoli-Calmettes, Laboratory of Molecular Pharmacology, 27 Boulevard Leï Roure, 13009 Marseille, France
2Centre for Neuroscience Research, Division of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh EH8 9JZ, UK.

Abstract: Protein-protein interactions are key elements in building functional protein complexes. Among the plethora of domains identified during the last 10 years, PDZ domains are one of the most commonly found protein-protein interaction domains in organisms from bacteria to humans. Although they may be the sole protein interaction domain within a cytoplasmic protein, they are most often found in combination with other protein interaction domains (for instance, SH3, PTB, WW) participating in complexes that facilitate signaling or determine the localization of receptors. Diversity of PDZ-containing protein function is provided by the large number of PDZ proteins that Mother Nature has distributed in the genome and implicates this protein family in the wiring of a huge number of molecules in molecular networks from the plasma membrane to the nucleus. Although at first sight their binding specificity appeared rather monotonous, involving only binding to the carboxyl-terminus of various proteins, it is now recognized that PDZ domains interact with greater versatility through PDZ-PDZ domain interaction; they bind to internal peptide sequences and even to lipids. Furthermore, PDZ domain-mediated interactions can sometimes be modulated in a dynamic way through target phosphorylation. In this review, we attempt to describe the structural basis of PDZ domain recognition and to give some functional insights into their role in the scaffolding of protein complexes implicated in normal and pathological biological processes.

*Corresponding author: Telephone, 33-4-91-75-84-09; fax, 33-4-91-26-03-64; e-mail: borg{at}marseille.inserm.fr

Citation: C. Nourry, S. G. N. Grant, J.-P. Borg, PDZ Domain Proteins: Plug and Play! Sci. STKE 2003, re7 (2003).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
RNAi screening identifies mediators of NOD2 signaling: Implications for spatial specificity of MDP recognition.
S. Lipinski, N. Grabe, G. Jacobs, S. Billmann-Born, A. Till, R. Hasler, K. Aden, M. Paulsen, A. Arlt, L. Kraemer, et al. (2012)
PNAS 109, 21426-21431
   Abstract »    Full Text »    PDF »
Ligation of erythrocyte CR1 induces its clustering in complex with scaffolding protein FAP-1.
I. Ghiran, A. M. Glodek, G. Weaver, L. B. Klickstein, and A. Nicholson-Weller (2008)
Blood 112, 3465-3473
   Abstract »    Full Text »    PDF »
PDZ Domain Binding Selectivity Is Optimized Across the Mouse Proteome.
M. A. Stiffler, J. R. Chen, V. P. Grantcharova, Y. Lei, D. Fuchs, J. E. Allen, L. A. Zaslavskaia, and G. MacBeath (2007)
Science 317, 364-369
   Abstract »    Full Text »    PDF »
Mint-3 Regulates the Retrieval of the Internalized Membrane-type Matrix Metalloproteinase, MT5-MMP, to the Plasma Membrane by Binding to Its Carboxyl End Motif EWV.
P. Wang, X. Wang, and D. Pei (2004)
J. Biol. Chem. 279, 20461-20470
   Abstract »    Full Text »    PDF »
Assembly of Cell Regulatory Systems Through Protein Interaction Domains.
T. Pawson and P. Nash (2003)
Science 300, 445-452
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882