Recent advances in large-scale protein interactome mapping

Abstract

Protein-protein interactions (PPIs) underlie most, if not all, cellular functions. The comprehensive mapping of these complex networks of stable and transient associations thus remains a key goal, both for systems biology-based initiatives (where it can be combined with other 'omics' data to gain a better understanding of functional pathways and networks) and for focused biological studies. Despite the significant challenges of such an undertaking, major strides have been made over the past few years. They include improvements in the computation prediction of PPIs and the literature curation of low-throughput studies of specific protein complexes, but also an increase in the deposition of high-quality data from non-biased high-throughput experimental PPI mapping strategies into publicly available databases.

Keywords: AP-MS; APEX; BioID; Interactome; PCP; Proteomics; XL-MS; affinity purification-mass spectrometry; cross-linking MS analysis; protein correlation profiling.

Figure 1.. Examples of experimental approaches used to map protein-protein interactions.

a. Affinity purification-mass spectrometry approach for identifying proteins that associate with a particular bait protein. b. Two spatially-restricted “near neighbor labeling” approaches that utilize enzymatic reactions to tag proteins (for capture and identification) that associate with a bait protein. c. Strategy behind cross-linking mass spectrometry analysis of multiprotein complexes. d. Protein correlation profiling approach for identifying multiprotein complex members that co-elute following various separation techniques. e. Strategy behind the classic yeast two-hybrid method used to screen for direct protein-protein interactions.