The Penicillin sensory transducer, blar, involved in the inducibility of beta-lactamase synthesis in bacillus licheniformis is embedded in the plasma membrane via a four-alpha-helix bundle
[en] Prediction studies, conformational analyses and membrane-topology mapping lead to the conclusion that the penicillin sensory transducer, BlaR, involved in the inducibility of beta-lactamase synthesis in Bacillus licheniformis, is embedded in the plasma membrane bilayer via four transmembrane segments TM1-TM4 that forma four-alpha-helix bundle. The extracellular 262-amino-acid-residue polypeptide, S340-R601, that is fused at the carboxy end of TM4, possesses the amino acid sequence signature of a penicilloyl serine transferase. It probably functions as penicillin sensor. As an independent entity, this polypeptide behaves as a high-affinity penicillin-binding protein. As a component of the full-size BlaR, it adopts a different conformation presumably because of interactions with the extracellular 63-amino-acid-residue P53-S115 loop that connects TM2 and TM3.
Reception of the penicillin-induced signal requires a precise conformation of the sensor but it does not involve penicilloylation of the serine residue S402 of motif STYK. Signal transmission through the plasma membrane by the four-alpha-helix bundle may proceed in a way comparable to that of the aspartate receptor, Tar. Signal emission in the cytosol by the intracellular 189-amino-acid-residue Y134-K322 loop that connects TM3 and TM4, may proceed via the activation of a putative metallopeptidase.
Research center :
CIP - Centre d'Ingénierie des Protéines - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Hardt, Karin; Université de Liège - ULiège > Centre d'ingéniérie des protéines
Joris, Bernard ; Université de Liège - ULiège > Physiologie et génétique bactériennes
Lepage, Sophie; Université de Liège - ULiège > Institut de Chimie > Centre d'ingénierie des Protéines
Brasseur, Robert ; Université de Liège - ULiège > Gembloux Agro-Bio Tech
Lampen, J. Olivier; State University of New Jersey > Waksman Institute
Frère, Jean-Marie ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Fink, Anthony L.; University of California > Department of Chemistry and Biochemistry
Ghuysen, Jean-Marie ; Université de Liège - ULiège > Centre d'ingénierie des protéines
Language :
English
Title :
The Penicillin sensory transducer, blar, involved in the inducibility of beta-lactamase synthesis in bacillus licheniformis is embedded in the plasma membrane via a four-alpha-helix bundle
Publication date :
1997
Journal title :
Molecular Microbiology
ISSN :
0950-382X
eISSN :
1365-2958
Publisher :
Blackwell Publishing, Oxford, United Kingdom
Volume :
23
Issue :
5
Pages :
935-944 935-944
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FRFC - Fonds de la Recherche Fondamentale Collective [BE] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Andersson, H., and von Heijne, G. (1993) Sec dependent and sec independent assembly of E. coli inner membrane proteins: the topological rules depend on chain length. EMBO J 12: 683-691.
Baneyx, F., and Georgiou, G. (1990) In vivo degradation of secreted fusion proteins by the Escherichia coli outer membrane protease OmpT. J Bacteriol 172: 491-494.
Baneyx, F., and Georgiou, G. (1991) Construction and characterization of Escherichia coli strains deficient in multiple secreted proteases: protease III degrades high-molecularweight substrates in vivo. J Bacteriol 173: 2696-2703.
Brasseur, R. (1991) Differentiation of lipid-associating helices by use of three-dimensional molecular hydrophobicity potential calculations. J Biol Chem 266: 16120-16127.
Broome-Smith, J.K., Tadayyon, M., and Zhang, Y. (1990) Beta-lactamase as a probe of membrane protein assembly and protein export. Mol Microbiol 4: 1637-1644.
Claros, G., and von Heijne, G. (1994) TOPPRED II: an improved software for membrane protein structure predictions. CABIOS 10: 685-686.
De Boer, W.R., Kruyssen, F.J., and Wouters, J.T.M. (1981) Cell wall turnover in batch and chemostat cultures of Bacillus subtilis. J Bacteriol 145: 50-60.
Eisenberg, D. (1984) Three-dimensional structure of membrane and surface proteins. Annu Rev Biochem 53: 595-623.
Ghuysen, J.M. (1994) Molecular structures of penicillin-binding proteins and ß-lactamases. Trends Microbiol 2: 372-380.
Ghuysen, J.M., Charlier, P., Coyette, J., Duez, C., Fonzé, E., Fraipont, C., Goffin, C., Joris, B., and Nguyen-Disteche, M. (1996) Penicillin and beyond: evolution, protein fold, multimodular polypeptides, and multiprotein complexes. Microb Drug Res 2: 163-175.
Gierash, L.M. (1989) Signal sequences. Biochemistry 28: 923-930.
von Heijne, G. (1992) Membrane protein structure prediction. Hydrophobicity analysis and the positive-inside rule. J Mol Biol 225: 487-494.
von Heijne, G., and Manoil, C. (1990) Membrane proteins: from sequence to structure. Protein Eng 4: 109-112.
Jacobs, C., Huang, L., Bartowsky, E., Normark, S., and Park, J.T. (1994) Bacterial cell wall recycling provides cytosolic muropeptides as effectors for β-lactamase induction. EMBO J 13: 4684-4694.
Jacobs, C., Joris, B., Jamin, M., van Beeumen, J., van Heijenoort, J., Park, J.T., Normark, S., and Frère, J.M. (1995) AmpD, essential for both β-lactamase regulation and cell wall recycling, is a novel cytosolic N-acetylmuramyl-L-alanine amidase. Mol Microbiol 15: 553-559.
Joris, B., Ledent, P., Kobayashi, T., Lampen, J.O., and Ghuysen, J.M. (1990) Expression in Escherichia coli of the Met346-Arg601 carboxy terminal domain of the BLAR sensory transducer protein of Bacillus licheniformis as a water-soluble 26000-Mr penicillin-binding protein. FEMS Microbiol Lett 70: 107-113.
Joris, B., Hardt, K., and Ghuysen, J.M. (1994) Induction of ßlactamase and low-affinity penicillin-binding protein 2′ synthesis in Gram-positive bacteria. New Comprehensive Biochem 27: 505-515.
Kobayashi, T., Zhu, Y.F., Nicholls, N., and Lampen, J.O. (1987) A second regulatory gene, blaR1, encoding a potential penicillin-binding protein required for induction of β-lactamase in Bacillus licheniformis. J Bacteriol 169: 3873-3878.
Lindström, E.B., Boman, H.G., and Steele, B.B. (1970) Resistance of Escherichia coli to penicillins. J Bacteriol 101:218-231.
Lynch, B.A., and Koshland, D.E. (1991) Disulfide crosslinking studies of the transmembrane regions of the aspartate sensory receptor of Escherichia coli. Proc Natl Acad Sci USA 88: 10741-10410.
Mengin-Lecreulx, D., van Heijenoort, J., and Park, J.T. (1996) Identification of the mp/gene encoding UDP-N-acetylmuramate: L-alanyl-γ-D-glutamyl-meso-diaminopimelate ligase in Escherichia coli and its role in recycling of cell wall peptidoglycan. J Bacteriol 178: 5347-5352.
Milburn, M.V., Privé, G.G., Milligan, D.L., Scott, W.G., Yeh, J., Jancarik, J., Koshland, D.E., Jr, and Kim, S.-H. (1991) Three-dimensional structures of the ligand-binding domain of the bacterial aspartate receptor with and without a ligand. Science 254: 1342-1347.
O'Callaghan, C.H., Morris, A., Kirby, S.M., and Shingler, A.M. (1972) Novel method for detection of β-lactamase by using a chromogenic cephalosporin substrate. Antimicrob Ag Chemother 1:283-288.
Park, J.T. (1996) The convergence of murein recycling research with β-lactamase research. Microb Drug Resistance 2: 105-112.
Quax, W. (1990) B. licheniformis protoplast transformation. In Molecular Biological Methods for Bacillus. Harwood, C.R., and Cutting, S. (eds). New York: John Wiley, pp. 152-153.
Sambrook, J., Fritsh, E.F., and Maniatis, T. (1989) Molecular Cloning: A Laboratory Manual. 2nd edn. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press.
Surette, M.G., and Stock, J.B. (1994) Transmembrane signal transducing proteins. New Comprehensive Biochem 27: 465-483.
Takagi, M., Ohta, T., Johki, S., and Imanaka, T. (1993) Characterization of the membrane sensor PenJ for β-lactam antibiotics from Bacillus licheniformis by amino acid substitution. FEMS Microbiol Lett 110: 127-132.
Tomoyasu, T., Gamer, J., Bukau, B., Kanemori, M., Mori, H., Rutman, A.J., Oppenheim, A.B., Yura, T., Yamanaka, K., Nike, H., Hiraga, S., and Ogura, T. (1995) Escherichia coli FtsH is a membrane-bound, ATP-dependent protease which degrades the heat-shock transcription factor σr32. EMBO J 14: 2551-2560.
Vallee, B.L., and Auld, D.S. (1992) Functional zinc-binding motifs in enzymes and DNA-binding proteins. Faraday Discuss 93: 47-65.
Zhu, Y.F., Curran, I.H.A., Joris, B., Ghuysen, J.M., and Lampen, J.O. (1990) Identification of BIaR, the signal transducer for β-lactamase production in Bacillus licheniformis, as a penicillin-binding protein with strong homology to the OXA-2 β-lactamase (class D) of Salmonella typhimurium. J Bacteriol 172: 1137-1141.
Zhu, Y.F., Englebert, S., Joris, B., Ghuysen, J.M., Kobayashi, T., and Lampen, J.O. (1992) Structure, function, and fate of the BIaR signal transducer involved in induction of β-lactamase in Bacillus licheniformis. J Bacteriol 174: 6171-6178.
