The human PDZome: a gateway to PSD95-Disc large-zonula occludens (PDZ)-mediated functions.
Mol Cell Proteomics. 2013-05-30; 12(9): 2587-2603
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1. Mol Cell Proteomics. 2013 Sep;12(9):2587-603. doi: 10.1074/mcp.O112.021022. Epub
2013 May 30.
The human PDZome: a gateway to PSD95-Disc large-zonula occludens (PDZ)-mediated
Belotti E(1), Polanowska J, Daulat AM, Audebert S, Thomé V, Lissitzky JC, Lembo
F, Blibek K, Omi S, Lenfant N, Gangar A, Montcouquiol M, Santoni MJ, Sebbagh M,
Aurrand-Lions M, Angers S, Kodjabachian L, Reboul J, Borg JP.
(1)CRCM, Equipe labellisée Ligue Contre le Cancer, Inserm, U1068, CRCM,
Marseille, F-13009, France.
Protein-protein interactions organize the localization, clustering, signal
transduction, and degradation of cellular proteins and are therefore implicated
in numerous biological functions. These interactions are mediated by specialized
domains able to bind to modified or unmodified peptides present in binding
partners. Among the most broadly distributed protein interaction domains,
PSD95-disc large-zonula occludens (PDZ) domains are usually able to bind
carboxy-terminal sequences of their partners. In an effort to accelerate the
discovery of PDZ domain interactions, we have constructed an array displaying 96%
of the human PDZ domains that is amenable to rapid two-hybrid screens in yeast.
We have demonstrated that this array can efficiently identify interactions using
carboxy-terminal sequences of PDZ domain binders such as the E6 oncoviral protein
and protein kinases (PDGFRβ, BRSK2, PCTK1, ACVR2B, and HER4); this has been
validated via mass spectrometry analysis. Taking advantage of this array, we show
that PDZ domains of Scrib and SNX27 bind to the carboxy-terminal region of the
planar cell polarity receptor Vangl2. We also have demonstrated the requirement
of Scrib for the promigratory function of Vangl2 and described the morphogenetic
function of SNX27 in the early Xenopus embryo. The resource presented here is
thus adapted for the screen of PDZ interactors and, furthermore, should
facilitate the understanding of PDZ-mediated functions.
PMID: 23722234 [Indexed for MEDLINE]