Site-2 proteases in prokaryotes: regulated intramembrane proteolysis expands to microbial pathogenesis

Makinoshima, Hideki; Glickman, Michael S.

doi:10.1016/j.micinf.2006.02.021

Cited by 49 publications

(35 citation statements)

References 48 publications

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“…They possess conserved amino acid sequence motifs, a typical zinc metalloprotease motif HEXXH, and a C-terminal-located LDG motif (5,6). Mutational alterations of the conserved residues in these motifs abolish the proteolytic activities (7)(8)(9), in agreement with the prediction that these motifs constitute a protease active site (10).…”

supporting

confidence: 75%

“…Complementation Assays-KK31 (a ⌬rseP strain having pKK6 with ara-controlled rseP) was transformed further with a plasmid carrying the wild type or mutant forms of lac-controlled rseP-his 6 -myc and grown in L-arabinose (0.2%) at 30°C. The cultures were serially diluted with 0.9% saline, and portions of the diluted cultures were spotted on L agar plates containing 1 mM isopropyl-1-thio-␤-D-galactopyranoside (test plates) or 0.2% arabinose (control plates) and incubated at 30°C.…”

Section: Methodsmentioning

confidence: 99%

“…The S2P family proteases are widely distributed from bacteria to higher organisms and involved in diverse biological processes (5,6). They possess conserved amino acid sequence motifs, a typical zinc metalloprotease motif HEXXH, and a C-terminal-located LDG motif (5,6).…”

mentioning

confidence: 99%

“…Caulobacter crescentus MmpA participates in cell polarity determination (15). Recent studies showed that S2P homologs of Vibrio cholerae and Mycobacterium tuberculosis (YaeL and Rv2869c, respectively) are involved in the pathogenic activities of these bacteria upon infection to host cells (6,16).…”

mentioning

confidence: 99%

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Environment of the Active Site Region of RseP, an Escherichia coli Regulated Intramembrane Proteolysis Protease, Assessed by Site-directed Cysteine Alkylation

Koide

Maegawa

Ito

et al. 2007

Journal of Biological Chemistry

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Regulated intramembrane proteolysis (RIP) plays crucial roles in both prokaryotic and eukaryotic organisms. Proteases for RIP cleave transmembrane regions of substrate membrane proteins. However, the molecular mechanisms for the proteolysis of membrane-embedded transmembrane sequences are largely unknown. Here we studied the environment surrounding the active site region of RseP, an Escherichia coli S2P ortholog involved in the E pathway of extracytoplasmic stress responses. RseP has two presumed active site motifs, HEXXH and LDG, located in membrane-cytoplasm boundary regions. We examined the reactivity of cysteine residues introduced within or in the vicinity of these two active site motifs with membrane-impermeable thiol-alkylating reagents under various conditions. The active site positions were inaccessible to the reagents in the native state, but many of them became partially modifiable in the presence of a chaotrope, while requiring simultaneous addition of a chaotrope and a detergent for full modification. These results suggest that the active site of RseP is not totally embedded in the lipid phase but located within a proteinaceous structure that is partially exposed to the aqueous milieu.Proteases contribute to functional regulation of some membrane proteins by introducing specific cleavages into them. For example, eukaryotic membrane-bound proteases such as ADAMs (a disintegrin and metalloproteinase) catalyze ectodomain shedding in which they cleave off extracellular domains of membrane proteins, including cytokines, growth factors, and adhesion molecules (1, 2). Membrane-embedded proteases are also involved in regulated intramembrane proteolysis (RIP) 2 , in which regulated cleavages are introduced into transmembrane segments of membrane proteins. An increasing number of findings have revealed that RIP plays pivotal roles in cell regulation and transmembrane signaling (3, 4). Proteases engaged in RIP include the S2P protease ␥-secretase, the rhomboid protease, and the signal peptide peptidase (3, 4). The S2P family proteases are widely distributed from bacteria to higher organisms and involved in diverse biological processes (5, 6). They possess conserved amino acid sequence motifs, a typical zinc metalloprotease motif HEXXH, and a C-terminal-located LDG motif (5, 6). Mutational alterations of the conserved residues in these motifs abolish the proteolytic activities (7-9), in agreement with the prediction that these motifs constitute a protease active site (10). The mammalian S2P protease, a founding member of RIP proteases, is an integral component of the regulatory systems for sterol metabolism and endoplasmic reticulum stress responses (11,12). In prokaryotes, two S2P homologs of Bacillus subtilis, SpoIVFB (13) and YluC (14), control sporulation and environmental stress responses, respectively. Caulobacter crescentus MmpA participates in cell polarity determination (15). Recent studies showed that S2P homologs of Vibrio cholerae and Mycobacterium tuberculosis (YaeL and Rv2869c, respectively) are i...

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supporting

confidence: 75%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Environment of the Active Site Region of RseP, an Escherichia coli Regulated Intramembrane Proteolysis Protease, Assessed by Site-directed Cysteine Alkylation

Koide

Maegawa

Ito

et al. 2007

Journal of Biological Chemistry

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“…Related to Lmo1318 is Lmo2563, which is also predicted to be a S2P/M50 peptidase albeit without a PDZ domain and sharing similarities with the B. subtilis sporulation factor SpoIVFB (35). Interestingly, S2P/M50 proteases, by catalyzing cleavage of membrane-bound proteins, seem to be involved in a variety signal transduction pathways, some off which play roles in host-pathogen interaction (117). Whether Lmo1851, Lmo1318, and Lmo2563 function as cell surface proteases will require further investigation.…”

Section: Protein Processing Folding and Anchoringmentioning

confidence: 99%

Listeria monocytogenesSurface Proteins: from Genome Predictions to Function

Bierne

Cossart

2007

Microbiol Mol Biol Rev

208

257

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SUMMARY The genome of the human food-borne pathogen Listeria monocytogenes is predicted to encode a high number of surface proteins. This abundance likely reflects the ability of this bacterium to survive in diverse environments, including soil, food, and the human host. This review focuses on the various mechanisms by which listerial proteins are attached at the bacterial surface and their many functions, including peptidoglycan metabolism, protein processing, adhesion to host cells, and invasion of host tissues. Extensive in silico analysis of the domains or motifs present in these mosaic proteins reveals that diverse structural features allow the surface proteome to interact with diverse bacterial or host components. This diversity offers new clues about the molecular bases of Listeria pathogenesis.

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