A conserved extended signal peptide region directs posttranslational protein translocation via a novel mechanism.
Members of the type V secretion family are among the most prevalent secreted proteins in Gram-negative bacteria. A subset of this family, including Pet, the prototypical member of the Enterobacteriaceae serine proteases, possess unusual signal peptides which can be divided into five regions termed N1 (charged), H1 (hydrophobic), N2, H2 and C (cleavage site) domains. The N1 and H1 regions, which the authors have named the extended signal peptide region (ESPR), demonstrate remarkable conservation. In contrast, the N2, H2 and C regions show significant variability, and are reminiscent of typical Sec-dependent signal sequences. Despite several investigations, the function of the ESPR remains obscure. Here, it is shown that proteins possessing the ESPR are translocated in a posttranslational fashion. The presence of the ESPR severely impairs inner membrane translocation. Mutational analysis suggests that the ESPR delays inner membrane translocation by adopting a particular conformation, or by interacting with a cytoplasmic or inner membrane co-factor, prior to inner membrane translocation.
Desvaux
Mickaël
M
Division of Immunity and Infection, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
Scott-Tucker
Anthony
A
Turner
Sue M
SM
Cooper
Lisa M
LM
Huber
Damon
D
Nataro
James P
JP
Henderson
Ian R
IR
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D004755:Enterobacteriaceae / Q000378:metabolism*; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D017434:Protein Structure, Tertiary / Q000502:physiology*; D021381:Protein Transport; D012697:Serine Endopeptidases / Q000737:chemistry / Q000378:metabolism*
D001426:Bacterial Proteins; D012697:Serine Endopeptidases