Dimer recognition and secretion by the ESX secretion system in Bacillus subtilis.
Protein secretion typically involves translocation of unfolded polypeptides or transport of monomeric folded proteins. Here we provide, to our knowledge, the first experimental evidence for secretion of an intact multimeric complex requiring a signal formed by both members of the complex. Using systematic mutagenesis of a substrate involved in early secretory antigen 6 kDa (ESX) secretion in Bacillus subtilis, we demonstrate that export of the substrate requires two independent motifs. Using mixed dimers, we show that these motifs must form a composite secretion signal in which one motif is contributed by each subunit of the dimer. Finally, through targeted crosslinking we show that the dimer formed in the cell is likely secreted as a single unit. We discuss implications of this substrate recognition mechanism for the biogenesis and quality control of secretion substrates and describe its likely conservation across ESX systems.
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.
Tatyana A
TA
Sysoeva
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.
Martha A
MA
Zepeda-Rivera
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138.
Laura A
LA
Huppert
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138 bburton@mcb.harvard.edu.
Briana M
BM
Burton
D001412:Bacillus subtilis / Q000235:genetics* / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism*; D058947:Bacterial Secretion Systems / Q000502:physiology*; D002850:Chromatography, Gel; D019281:Dimerization; D004591:Electrophoresis, Polyacrylamide Gel; D046912:Multiprotein Complexes / Q000378:metabolism*; D016296:Mutagenesis; D021381:Protein Transport / Q000502:physiology; D012394:Rosaniline Dyes
D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D046912:Multiprotein Complexes; D012394:Rosaniline Dyes; C048139:Coomassie blue
WXG protein; YukE; protein translocation; type VII secretion system