Determining protein complex connectivity using a probabilistic deletion network derived from quantitative proteomics.
Protein complexes are key molecular machines executing a variety of essential cellular processes. Despite the availability of genome-wide protein-protein interaction studies, determining the connectivity between proteins within a complex remains a major challenge. Here we demonstrate a method that is able to predict the relationship of proteins within a stable protein complex. We employed a combination of computational approaches and a systematic collection of quantitative proteomics data from wild-type and deletion strain purifications to build a quantitative deletion-interaction network map and subsequently convert the resulting data into an interdependency-interaction model of a complex. We applied this approach to a data set generated from components of the Saccharomyces cerevisiae Rpd3 histone deacetylase complexes, which consists of two distinct small and large complexes that are held together by a module consisting of Rpd3, Sin3 and Ume1. The resulting representation reveals new protein-protein interactions and new submodule relationships, providing novel information for mapping the functional organization of a complex.
Sardiu
Mihaela E
ME
Stowers Institute for Medical Research, Kansas City, Missouri, United States of America.
Gilmore
Joshua M
JM
Carrozza
Michael J
MJ
Li
Bing
B
Workman
Jerry L
JL
Florens
Laurence
L
Washburn
Michael P
MP
D016000:Cluster Analysis; D017353:Gene Deletion; D016678:Genome; D006655:Histone Deacetylases / Q000378:metabolism; D008954:Models, Biological; D015233:Models, Statistical; D011336:Probability; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry*; D040901:Proteomics / Q000379:methods*; D012097:Repressor Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
D011506:Proteins; D012097:Repressor Proteins; C071731:SIN3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C462439:UME1 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; D006655:Histone Deacetylases