title: High-throughput analysis of peptide-binding modules.
abstract: Modular protein interaction domains (PIDs) that recognize linear peptide motifs are found in hundreds of proteins within the human genome. Some PIDs such as SH2, 14-3-3, Chromo, and Bromo domains serve to recognize posttranslational modification (PTM) of amino acids (such as phosphorylation, acetylation, methylation, etc.) and translate these into discrete cellular responses. Other modules such as SH3 and PSD-95/Discs-large/ZO-1 (PDZ) domains recognize linear peptide epitopes and serve to organize protein complexes based on localization and regions of elevated concentration. In both cases, the ability to nucleate-specific signaling complexes is in large part dependent on the selectivity of a given protein module for its cognate peptide ligand. High-throughput (HTP) analysis of peptide-binding domains by peptide or protein arrays, phage display, mass spectrometry, or other HTP techniques provides new insight into the potential protein-protein interactions prescribed by individual or even whole families of modules. Systems level analyses have also promoted a deeper understanding of the underlying principles that govern selective protein-protein interactions and how selectivity evolves. Lastly, there is a growing appreciation for the limitations and potential pitfalls associated with HTP analysis of protein-peptide interactomes. This review will examine some of the common approaches utilized for large-scale studies of PIDs and suggest a set of standards for the analysis and validation of datasets from large-scale studies of peptide-binding modules. We will also highlight how data from large-scale studies of modular interaction domain families can provide insight into systems level properties such as the linguistics of selective interactions.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Liu
authors.forename: Brett W
authors.initials: BW
authors.lastname: Engelmann
authors.forename: Piers D
authors.initials: PD
authors.lastname: Nash
mesh_terms: D000818:Animals; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D040081:Protein Array Analysis; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D010455:Peptides; D011506:Proteins