Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.
One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans' biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a "systems-wide" functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins.
Hu
Pingzhao
P
Banting and Best Department of Medical Research, Terrence Donnelly Center for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario, Canada.
Janga
Sarath Chandra
SC
Babu
Mohan
M
Díaz-Mejía
J Javier
JJ
Butland
Gareth
G
Yang
Wenhong
W
Pogoutse
Oxana
O
Guo
Xinghua
X
Phanse
Sadhna
S
Wong
Peter
P
Chandran
Shamanta
S
Christopoulos
Constantine
C
Nazarians-Armavil
Anaies
A
Nasseri
Negin Karimi
NK
Musso
Gabriel
G
Ali
Mehrab
M
Nazemof
Nazila
N
Eroukova
Veronika
V
Golshani
Ashkan
A
Paccanaro
Alberto
A
Greenblatt
Jack F
JF
Moreno-Hagelsieb
Gabriel
G
Emili
Andrew
A
D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D016680:Genome, Bacterial; D046912:Multiprotein Complexes / Q000235:genetics; D025941:Protein Interaction Mapping / Q000379:methods; D020543:Proteome / Q000235:genetics*
D029968:Escherichia coli Proteins; D046912:Multiprotein Complexes; D020543:Proteome