title: Bacillus licheniformis BlaR1 L3 loop is a zinc metalloprotease activated by self-proteolysis.
abstract: In Bacillus licheniformis 749/I, BlaP β-lactamase is induced by the presence of a β-lactam antibiotic outside the cell. The first step in the induction mechanism is the detection of the antibiotic by the membrane-bound penicillin receptor BlaR1 that is composed of two functional domains: a carboxy-terminal domain exposed outside the cell, which acts as a penicillin sensor, and an amino-terminal domain anchored to the cytoplasmic membrane, which works as a transducer-transmitter. The acylation of BlaR1 sensor domain by the antibiotic generates an intramolecular signal that leads to the activation of the L3 cytoplasmic loop of the transmitter by a single-point cleavage. The exact mechanism of L3 activation and the nature of the secondary cytoplasmic signal launched by the activated transmitter remain unknown. However, these two events seem to be linked to the presence of a HEXXH zinc binding motif of neutral zinc metallopeptidases. By different experimental approaches, we demonstrated that the L3 loop binds zinc ion, belongs to Gluzincin metallopeptidase superfamily and is activated by self-proteolysis.
authors.affiliation: Centre for Protein Engineering, Department of Life Sciences, University of Liège, Liège, Belgium.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Berzigotti
authors.forename: Kamal
authors.initials: K
authors.lastname: Benlafya
authors.forename: Jérémy
authors.initials: J
authors.lastname: Sépulchre
authors.forename: Ana
authors.initials: A
authors.lastname: Amoroso
authors.forename: Bernard
authors.initials: B
authors.lastname: Joris
mesh_terms: D000595:Amino Acid Sequence; D001407:Bacillus / Q000201:enzymology* / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics; D001483:Base Sequence; D015153:Blotting, Western; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D059748:Proteolysis; D012394:Rosaniline Dyes; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000235:genetics*; D015032:Zinc / Q000378:metabolism; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D012394:Rosaniline Dyes; C048139:Coomassie blue; C569108:BlaR1 protein, Staphylococcus aureus; D008666:Metalloendopeptidases; D001618:beta-Lactamases; D015032:Zinc