Proteome-Scale Human Interactomics

Abstract

Cellular functions are mediated by complex interactome networks of physical, biochemical, and functional interactions between DNA sequences, RNA molecules, proteins, lipids, and small metabolites. A thorough understanding of cellular organization requires accurate and relatively complete models of interactome networks at proteome-scale. The recent publication of four human protein-protein interaction (PPI) maps represents a technological breakthrough and an unprecedented resource for the scientific community, heralding a new era of proteome-scale human interactomics. Our knowledge gained from these and complementary studies provides fresh insights into the opportunities and challenges when analyzing systematically generated interactome data, defines a clear roadmap towards the generation of a first reference interactome, and reveals new perspectives on the organization of cellular life.

Global Landscape of Native Protein Complexes inSynechocystissp. PCC 6803

“…The physical interactions between Sll0445 and photosynthetic proteins verified by the AP-MS experiment. The AP-MS also obtains other partners that not coordination with CoFrac-MS (Table S6).That might because different methods tend to catch different portions of physical interactions [41].…”

Protein Interaction Networks and Disease: Highlights of the 3rd Challenges in Computational Biology Meeting

“…Proteins participate in every cellular process and they do so through the interaction with other proteins [2]. As a result, perturbations of one or a few members of this intricate system propagate across the protein interaction network (PIN), disturbing its dynamics and deriving in abnormal phenotypes [3].…”

“…As a result, perturbations of one or a few members of this intricate system propagate across the protein interaction network (PIN), disturbing its dynamics and deriving in abnormal phenotypes [3]. Because of this, PINs have become the subject of intense investigation and there are several on-going projects aimed at constructing a reference, proteome-scale wiring diagram of the cell [2].…”

Towards an “assayome” for binary interactome mapping

“…Structural proteomics, which determines protein structures at proteome-scale 5 also requires a palette of technologies such as X-ray crystallography, nuclear magnetic resonance (NMR), and/or cryogenic electron microscopy (cryo-EM) to reasonably cover proteins and protein complexes of different sizes, solubilities, and flexibilities 6,7 .In short, the mapping of large macromolecular landscapes usually requires multiple technologies that can be combined to complement each other's relative shortcomings. However, for most comprehensive mapping projects, it remains unknown how to optimally combine various experimental methods in order to achieve maximal detection and specificity by a minimal number of assays.Macromolecules including DNA, RNA and proteins do not work in isolation but assemble into molecular machines, signaling cascades and metabolic pathways through interactions with other macromolecules, altogether forming complex interactome networks that are critical for biological 4 systems 8,9 . As protein-protein interactions (PPIs) play a pivotal role in these networks, it is essential to comprehensively identify binary PPIs 10-12 and co-complex protein associations [13][14][15] , both at the scale of signaling pathways 16,17 , molecular machines 18,19 and network modules 20 , and at the scale of the whole proteome 12 .Although medium-to high-throughput binary PPI detection assays have been available for three decades, since the original description of the yeast two-hybrid (Y2H) system 21 , it remains impossible to completely map interactome networks using any assay in isolation.…”