A structural portrait of the PDZ domain family.

Détails

ID Serval
serval:BIB_FBD3215FF1E9
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
A structural portrait of the PDZ domain family.
Périodique
Journal of Molecular Biology
Auteur(s)
Ernst A., Appleton B.A., Ivarsson Y., Zhang Y., Gfeller D., Wiesmann C., Sidhu S.S.
ISSN
1089-8638 (Electronic)
ISSN-L
0022-2836
Statut éditorial
Publié
Date de publication
2014
Peer-reviewed
Oui
Volume
426
Numéro
21
Pages
3509-3519
Langue
anglais
Résumé
PDZ (PSD-95/Discs-large/ZO1) domains are interaction modules that typically bind to specific C-terminal sequences of partner proteins and assemble signaling complexes in multicellular organisms. We have analyzed the existing database of PDZ domain structures in the context of a specificity tree based on binding specificities defined by peptide-phage binding selections. We have identified 16 structures of PDZ domains in complex with high-affinity ligands and have elucidated four additional structures to assemble a structural database that covers most of the branches of the PDZ specificity tree. A detailed comparison of the structures reveals features that are responsible for the diverse specificities across the PDZ domain family. Specificity differences can be explained by differences in PDZ residues that are in contact with the peptide ligands, but these contacts involve both side-chain and main-chain interactions. Most PDZ domains bind peptides in a canonical conformation in which the ligand main chain adopts an extended β-strand conformation by interacting in an antiparallel fashion with a PDZ β-strand. However, a subset of PDZ domains bind peptides with a bent main-chain conformation and the specificities of these non-canonical domains could not be explained based on canonical structures. Our analysis provides a structural portrait of the PDZ domain family, which serves as a guide in understanding the structural basis for the diverse specificities across the family.

Mots-clé
Binding Sites, Crystallography, X-Ray, Escherichia coli/metabolism, Humans, Ligands, PDZ Domains, Peptides/chemistry, Protein Binding, Protein Engineering/methods, Protein Interaction Mapping, Protein Structure, Secondary, Proteome, Proteomics/methods, Recombinant Proteins/chemistry, Sequence Homology, Amino Acid, Tight Junction Proteins/chemistry, Zonula Occludens-1 Protein/chemistry, ligand specificity, modular domains, peptide recognition, protein engineering, protein–protein interaction
Pubmed
Web of science
Création de la notice
15/12/2014 13:16
Dernière modification de la notice
20/08/2019 16:27
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