Probing Protein Interaction Networks by Combining MS-Based Proteomics and Structural Data Integration

Protein–protein
interactions play a major role in the molecular
machinery of life, and various techniques such as AP-MS are dedicated
to their identification. However, those techniques return lists of
proteins devoid of organizational structure, not detailing which proteins
interact with which others. Proposing a hierarchical view of the interactions
between the members of the flat list becomes highly tedious for large
data sets when done by hand. To help hierarchize this data, we introduce
a new bioinformatics protocol that integrates information of the multimeric
protein 3D structures available in the Protein Data Bank using remote
homology detection, as well as information related to Short Linear
Motifs and interaction data from the BioGRID. We illustrate on two
unrelated use-cases of different complexity how our approach can be
useful to decipher the network of interactions hidden in the list
of input proteins, and how it provides added value compared to state-of-the-art
resources such as Interactome3D or STRING. Particularly, we show the
added value of using homology detection to distinguish between orthologs
and paralogs, and to distinguish between core obligate and more facultative
interactions. We also demonstrate the potential of considering interactions
occurring through Short Linear Motifs.