Rhomboid protease AarA mediates quorum-sensing in
            <i>Providencia stuartii</i>
            by activating TatA of the twin-arginine translocase

Stevenson, Lindsay; Střı́šovský, Kvido; Clemmer, Katy M.; Bhatt, Shantanu; Freeman, Matthew; Rather, Philip N.

doi:10.1073/pnas.0608140104

Cited by 147 publications

(142 citation statements)

References 33 publications

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“…The natural substrates for prokaryotic and archaeal Rhomboid proteins are unknown, with one exception: Providencia stuartii Rhomboid protease AarA cleaves a protein called TatA as part of a quorum-sensing signal (32). As for eukaryotic Rhomboid proteins, two mitochondrial membrane proteins were identified as substrates for yeast Rhomboid Rbd1p (33)(34)(35).…”

Section: Rhomboid Serine Proteasesmentioning

confidence: 99%

Intramembrane-cleaving Proteases

Wolfe

2009

Journal of Biological Chemistry

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In the past decade or so, membrane-embedded proteases that carry out hydrolysis on the transmembrane region of their substrates have been discovered. These I-CLiPs 2 (1) somehow create an environment for water and the hydrophilic residues needed for catalysis and bend or unwind their helical substrates to make the amide bonds susceptible to hydrolysis. Despite the distinction of being membrane-embedded and cleaving TMDs, the residues essential for catalysis by these I-CLiPs are virtually the same as those found in aqueous proteases, clear examples of convergent evolution toward a common mechanism. Described herein are the different types of I-CLiPs and an update on their structural and mechanistic features and biological roles. S2P MetalloproteasesSREBPs are transcription factors that promote expression of genes involved in the synthesis of cholesterol and fatty acids (reviewed in Ref. 2). SREBPs are synthesized as a two-TMD precursor protein (Fig. 1A) that undergoes proteolytic release. The luminal loop between the two TMDs is first cleaved by the membrane-tethered S1P when cholesterol levels are low. Release of the transcription factor requires subsequent cleavage by S2P, which performs a hydrolysis three residues within the TMD. Complementation cloning identified S2P as a multipass membrane protein containing a conserved HEXXH sequence characteristic of zinc metalloproteases. Sequential processing by S1P and S2P likewise occurs for the transcription factor ATF6 during the ER stress response.The two histidines and the glutamate are required for S2P activity, consistent with known metalloprotease biochemistry in which the two histidines coordinate with zinc, the zinc activates the scissile amide bond, and the glutamate activates the catalytic water. A conserved aspartate located quite distant from HEXXH in the linear sequence is likewise critical for S2P activity and coordinates with the zinc atom (see below). Regarding the substrate, SREBP contains a conserved and helix-destabilizing asparagine-proline sequence within its TMD1 that is critical for proteolytic processing of the nearby leucine-cysteine bond by S2P.S2P-like proteases are also found in bacteria (3) and archaea (4). These prokaryotic proteins play an essential role in the proteolysis of membrane-bound transcription factors needed for sporulation, controlling gene expression in the mother cell after engulfment of the forespore. Cleavage of prok and release of the membrane-tethered transcription factor requires SpoIVFB in Bacillus subtilis. Another bacterial S2P family member, YaeL (also called RseP) in Escherichia coli, plays a role in coordinating cell growth and cell division through intramembrane proteolysis of RseA, a factor critical for responding to extracytoplasmic stress (5). Interestingly, the membrane orientations of substrates SREBP and k are opposite each other, correlating with those of their respective enzymes, S2P and SpoIVFB, which are similarly thought to have opposite orientations (3). This implies that the catalytic region must al...

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Section: Rhomboid Serine Proteasesmentioning

confidence: 99%

Intramembrane-cleaving Proteases

Wolfe

2009

Journal of Biological Chemistry

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“…In the bacterium Providencia stuartii, cleavage of a small inhibitory N-terminal peptide from the twin-arginine translocase TatA by the rhomboid protease AarA initiates quorum sensing by activating TatA's function as a channel for export of the quorumsensing signal [30,31]. Interestingly, most bacteria do not encode a TatA protein with an N-terminal extension and therefore do not have to be activated by cleavage, suggesting that the role of AarA is a rare adaptation rather than a general mechanism (reviewed in [32]).…”

Section: Role In Signallingmentioning

confidence: 99%

New insights into parasite rhomboid proteases

Santos

Graindorge

Soldati‐Favre

2012

Molecular and Biochemical Parasitology

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a b s t r a c tThe rhomboid-like proteins constitute a large family of intramembrane serine proteases that are present in all branches of life. First studied in Drosophila, these enzymes catalyse the release of the active forms of proteins from the membrane and hence trigger signalling events. In protozoan parasites, a limited number of rhomboid-like proteases have been investigated and some of them are associated to pathogenesis. In Apicomplexans, rhomboid-like protease activity is involved in shedding adhesins from the surface of the zoites during motility and host cell entry. Recently, a Toxoplasma gondii rhomboid was also implicated in an intracellular signalling mechanism leading to parasite proliferation. In Entamoeba histolytica, the capacity to adhere to host cells and to phagocytose cells is potentiated by a rhomboid-like protease. Survey of a small number of protozoan parasite genomes has uncovered species-specific rhomboidlike protease genes, many of which are predicted to encode inactive enzymes. Functional investigation of the rhomboid-like proteases in other protozoan parasites will likely uncover novel and unexpected implications for this family of proteases.

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“…8 -10). Besides the role of Drosophila rhomboid in growth factor signaling, rhomboid proteases have been found to be involved in quorum sensing in Providencia (11), in the functions of mitochondria such as membrane remodeling and apoptosis (12)(13)(14), and in the life cycle of apicomplexan parasites (15)(16)(17) by cleaving various membrane protein substrates.…”

mentioning

confidence: 99%

Catalytic Mechanism of Rhomboid Protease GlpG Probed by 3,4-Dichloroisocoumarin and Diisopropyl Fluorophosphonate

Xue

2012

Journal of Biological Chemistry

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Background:The rhomboid protease GlpG is a prototype of the serine intramembrane protease. Results: The crystal structure of GlpG in complex with diisopropyl fluorophosphonate was solved at 2.3 Å resolution. Conclusion:The crystal structure provides a model for the tetrahedral transitional state and reveals conformational changes within the active site. Significance: Learning how GlpG conducts catalysis is crucial for understanding the mechanism of intramembrane proteolysis by rhomboid proteases.

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Rhomboid protease AarA mediates quorum-sensing in Providencia stuartii by activating TatA of the twin-arginine translocase

Cited by 147 publications

References 33 publications

Intramembrane-cleaving Proteases

Intramembrane-cleaving Proteases

New insights into parasite rhomboid proteases

Catalytic Mechanism of Rhomboid Protease GlpG Probed by 3,4-Dichloroisocoumarin and Diisopropyl Fluorophosphonate

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