The BioPlex Network: A Systematic Exploration of the Human Interactome

Abstract

SUMMARY Protein interactions form a network whose structure drives cellular function and whose organization informs biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions among 7,668 proteins with 86% previously undocumented. BioPlex accurately depicts known complexes, attaining 80-100% coverage for most CORUM complexes. The network readily subdivides into communities that correspond to complexes or clusters of functionally related proteins. More generally, network architecture reflects cellular localization, biological process, and molecular function, enabling functional characterization of thousands of proteins. Network structure also reveals associations among thousands of protein domains, suggesting a basis for examining structurally-related proteins. Finally, BioPlex, in combination with other approaches can be used to reveal interactions of biological or clinical significance. For example, mutations in the membrane protein VAPB implicated in familial Amyotrophic Lateral Sclerosis perturb a defined community of interactors.

A role for Mitochondrial Rho GTPase 1 (MIRO1) in motility and membrane dynamics of peroxisomes

“…For MIRO1, PEX19 binding was shown by immunoprecipitation after co‐expression of Myc‐MIRO1 and HA‐PEX19 in COS‐7 cells (Figure 1B) suggesting a role for PEX19 in the targeting of MIRO1 to peroxisomes. Additionally, in a high‐throughput interaction study, MIRO1 was identified as a PEX19 interaction partner 37. These findings are also consistent with the known organelle targeting signals: MIRO1 possesses a transmembrane domain (TMD) with relatively low hydrophobicity (GRAVY, 1.3) and a moderate net charge in the tail region (1.9), which based on our previous work would be indicative of a TA protein that localises predominantly to mitochondria but has a potential for peroxisomal targeting 34.…”

Systematic autoantigen analysis identifies a distinct subtype of scleroderma with coincident cancer

“…The central finding of this study, that epitope spreading is a common feature of autoimmune responses, suggests that these genome-wide antigen discovery methods can be significantly improved by merging them computationally with proteomic approaches aimed at discovering protein complexes (14,15). Further studies using large, welldefined patient cohorts are warranted to understand the full Each row shows data corresponding to the candidate autoantigen gene listed in the first column.…”

Yeast Two-Hybrid Screening for Proteins that Interact with the Extracellular Domain of Amyloid Precursor Protein

“…1; for DNA sequences, see supplementary materials). Of the 9 candidates, TMEM30A was demonstrated to bind APP by affinity capture-MS [14]. Although RAB13 has not been demonstrated to bind with APP, 19 other RAB family proteins (RAB1B, RAB2B, RAB3A, RAB3D, RAB5C, RAB7B, RAB8B, RAB10, RAB11B, RAB14, RAB26, RAB27A, RAB28, RAB35, RAB38, RAB39A, RAB40B, RAB43, and RABL3) all interact with amyloid b [15].…”