| Structural highlights
Function
[RSEP_ECOLI] A site-2 regulated intramembrane protease (S2P) that cleaves the peptide bond between 'Ala-108' and 'Cys-109' in the transmembrane region of RseA. Part of a regulated intramembrane proteolysis (RIP) cascade. Acts on DegS-cleaved RseA to release the cytoplasmic domain of RseA, residue "Val-148" of RseA may be required for this. This provides the cell with sigma-E (RpoE) activity through the proteolysis of RseA. Can also cleave sequences in transmembrane regions of other proteins (such as LacY) as well as liberated signal peptides of beta-lactamase, OmpF, LivK, SecM, PhoA, LivJ, OmpC, Lpp and TorA, probably within the membrane.[1] [2] [3] [4] [5] [6] [7]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Regulated intramembrane proteolysis (RIP) by the Site-2 protease (S2P) results in the release of a transmembrane signaling protein. Curiously, however, S2P cleavage must be preceded by the action of the Site-1 protease (S1P). To decipher the underlying mechanism, we reconstituted sequential, in vitro cleavages of the Escherichia coli transmembrane protein RseA by DegS (S1P) and RseP (S2P). After DegS cleavage, the newly exposed carboxyl-terminal residue Val-148 of RseA plays an essential role for RseP cleavage, and its mutation to charged or dissimilar amino acids crippled the Site-2 cleavage. By contrast, the identity of residues 146 and 147 of RseA has no impact on Site-2 cleavage. These results explain why Site-1 cleavage must precede Site-2 cleavage. Structural analysis reveals that the putative peptide-binding groove in the second, but not the first, PDZ domain of RseP is poised for binding to a single hydrophobic amino acid. These observations suggest that after DegS cleavage, the newly exposed carboxyl terminus of RseA may facilitate Site-2 cleavage through direct interaction with the PDZ domain.
Cleavage of RseA by RseP requires a carboxyl-terminal hydrophobic amino acid following DegS cleavage.,Li X, Wang B, Feng L, Kang H, Qi Y, Wang J, Shi Y Proc Natl Acad Sci U S A. 2009 Aug 17. PMID:19706448[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kanehara K, Akiyama Y, Ito K. Characterization of the yaeL gene product and its S2P-protease motifs in Escherichia coli. Gene. 2001 Dec 27;281(1-2):71-9. PMID:11750129
- ↑ Kanehara K, Ito K, Akiyama Y. YaeL (EcfE) activates the sigma(E) pathway of stress response through a site-2 cleavage of anti-sigma(E), RseA. Genes Dev. 2002 Aug 15;16(16):2147-55. PMID:12183368 doi:http://dx.doi.org/10.1101/gad.1002302
- ↑ Alba BM, Leeds JA, Onufryk C, Lu CZ, Gross CA. DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response. Genes Dev. 2002 Aug 15;16(16):2156-68. PMID:12183369 doi:10.1101/gad.1008902
- ↑ Akiyama Y, Kanehara K, Ito K. RseP (YaeL), an Escherichia coli RIP protease, cleaves transmembrane sequences. EMBO J. 2004 Nov 10;23(22):4434-42. Epub 2004 Oct 21. PMID:15496982 doi:http://dx.doi.org/7600449
- ↑ Koide K, Ito K, Akiyama Y. Substrate recognition and binding by RseP, an Escherichia coli intramembrane protease. J Biol Chem. 2008 Apr 11;283(15):9562-70. doi: 10.1074/jbc.M709984200. Epub 2008 , Feb 11. PMID:18268014 doi:http://dx.doi.org/10.1074/jbc.M709984200
- ↑ Saito A, Hizukuri Y, Matsuo E, Chiba S, Mori H, Nishimura O, Ito K, Akiyama Y. Post-liberation cleavage of signal peptides is catalyzed by the site-2 protease (S2P) in bacteria. Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13740-5. doi:, 10.1073/pnas.1108376108. Epub 2011 Aug 2. PMID:21810987 doi:http://dx.doi.org/10.1073/pnas.1108376108
- ↑ Inaba K, Suzuki M, Maegawa K, Akiyama S, Ito K, Akiyama Y. A pair of circularly permutated PDZ domains control RseP, the S2P family intramembrane protease of Escherichia coli. J Biol Chem. 2008 Dec 12;283(50):35042-52. doi: 10.1074/jbc.M806603200. Epub 2008, Oct 22. PMID:18945679 doi:http://dx.doi.org/10.1074/jbc.M806603200
- ↑ Li X, Wang B, Feng L, Kang H, Qi Y, Wang J, Shi Y. Cleavage of RseA by RseP requires a carboxyl-terminal hydrophobic amino acid following DegS cleavage. Proc Natl Acad Sci U S A. 2009 Aug 17. PMID:19706448
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