Crystal Structure of a Bacterial Signal Peptide Peptidase

Journal Article · Tue Jan 01 04:00:00 EST 2008 · Journal of Molecular Biology

DOI:https://doi.org/10.1016/j.jmb.2007.11.080· OSTI ID:959746

Kim, A; Oliver, D; Paetzel, M

Signal peptide peptidase (Spp) is the enzyme responsible for cleaving the remnant signal peptides left behind in the membrane following Sec-dependent protein secretion. Spp activity appears to be present in all cell types, eukaryotic, prokaryotic and archaeal. Here we report the first structure of a signal peptide peptidase, that of the Escherichia coli SppA (SppAEC). SppAEC forms a tetrameric assembly with a novel bowl-shaped architecture. The bowl has a dramatically hydrophobic interior and contains four separate active sites that utilize a Ser/Lys catalytic dyad mechanism. Our structural analysis of SppA reveals that while in many Gram-negative bacteria as well as characterized plant variants, a tandem duplication in the protein fold creates an intact active site at the interface between the repeated domains, other species, particularly Gram-positive and archaeal organisms, encode half-size, unduplicated SppA variants that could form similar oligomers to their duplicated counterparts, but using an octamer arrangement and with the catalytic residues provided by neighboring monomers. The structure reveals a similarity in the protein fold between the domains in the periplasmic Ser/Lys protease SppA and the monomers seen in the cytoplasmic Ser/His/Asp protease ClpP. We propose that SppA may, in addition to its role in signal peptide hydrolysis, have a role in the quality assurance of periplasmic and membrane-bound proteins, similar to the role that ClpP plays for cytoplasmic proteins.

• Research Organization: Brookhaven National Laboratory (BNL) National Synchrotron Light Source
• Sponsoring Organization: Doe - Office Of Science
• DOE Contract Number: AC02-98CH10886
• OSTI ID: 959746
• Report Number(s): BNL--82732-2009-JA
• Journal Information: Journal of Molecular Biology, Journal Name: Journal of Molecular Biology Vol. 376; ISSN JMOBAK; ISSN 0022-2836
• Country of Publication: United States
• Language: English

Related Subjects

36 MATERIALS SCIENCE
ARCHITECTURE
BACTERIA
CRYSTAL STRUCTURE
ENZYMES
ESCHERICHIA COLI
HYDROLYSIS
MEMBRANES
MONOMERS
PEPTIDES
PROTEINS
QUALITY ASSURANCE
RESIDUES
SECRETION
national synchrotron light source