Identifying cognate binding pairs among a large set of paralogs: the case of PE/PPE proteins of Mycobacterium tuberculosis.
We consider the problem of how to detect cognate pairs of proteins that bind when each belongs to a large family of paralogs. To illustrate the problem, we have undertaken a genomewide analysis of interactions of members of the PE and PPE protein families of Mycobacterium tuberculosis. Our computational method uses structural information, operon organization, and protein coevolution to infer the interaction of PE and PPE proteins. Some 289 PE/PPE complexes were predicted out of a possible 5,590 PE/PPE pairs genomewide. Thirty-five of these predicted complexes were also found to have correlated mRNA expression, providing additional evidence for these interactions. We show that our method is applicable to other protein families, by analyzing interactions of the Esx family of proteins. Our resulting set of predictions is a starting point for genomewide experimental interaction screens of the PE and PPE families, and our method may be generally useful for detecting interactions of proteins within families having many paralogs.
Riley
Robert
R
Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, United States of America.
Pellegrini
Matteo
M
Eisenberg
David
D
D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics; D019295:Computational Biology; D003198:Computer Simulation; D004926:Escherichia coli / Q000235:genetics; D019143:Evolution, Molecular; D015870:Gene Expression; D016680:Genome, Bacterial; D008957:Models, Genetic; D046912:Multiprotein Complexes; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000378:metabolism* / Q000472:pathogenicity; D009876:Operon; D010802:Phylogeny; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping / Q000706:statistics & numerical data*; D012329:RNA, Bacterial / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D001426:Bacterial Proteins; D046912:Multiprotein Complexes; D012329:RNA, Bacterial; D012333:RNA, Messenger
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