Crystal structure of the sensor domain of the BlaR penicillin receptor from Bacillus licheniformis.
As in several staphylococci, the synthesis of the Bacillus licheniformis 749/I beta-lactamase is an inducible phenomenon regulated by a signal-transducing membrane protein BlaR. The C-terminal domain of this multimodular protein is an extracellular domain which specifically recognizes beta-lactam antibiotics. When it binds a beta-lactam, a signal is transmitted by the transmembrane region to the intracellular loops. In response, the hydrolytic activity of the BlaR large cytoplasmic L3 loop is induced, and a cascade of reactions is generated, leading to the transcription of the beta-lactamase gene. Here, we describe the crystal structure of the extracellular penicillin-receptor domain of BlaR (residues 346-601) at 2.5 A resolution in order to understand why this domain, whose folding is very similar to that of class D beta-lactamases, behaves as a highly sensitive penicillin-binding protein rather than a beta-lactamase. Two residues of the BlaR C-terminal domain, Thr452 and Thr542, modify the hydrophobic characteristic of the class D beta-lactamase active site. Both residues seem to be in part responsible for the lack of beta-lactamase activity of the BlaR protein due to the stability of the acyl-enzyme. Although further experimental data are needed to fully understand the transmembrane induction process, the comparison of the BlaR sensor domain structure with those of class D beta-lactamase complexes and penicillin-binding proteins provides interesting elements to hypothesize on possible signal transmission mechanisms.
Institut de Physique B5, Université de Liège, B-4000 Sart Tilman, Belgium.
Frédéric
F
Kerff
Paulette
P
Charlier
Maria-Luigi
ML
Colombo
Eric
E
Sauvage
Alain
A
Brans
Jean-Marie
JM
Frère
Bernard
B
Joris
Eveline
E
Fonzé
D000215:Acylation; D000595:Amino Acid Sequence; D001407:Bacillus / Q000737:chemistry*; D001426:Bacterial Proteins / Q000737:chemistry*; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry*; D003460:Crystallization; D018360:Crystallography, X-Ray; D007700:Kinetics; D008969:Molecular Sequence Data; D046915:Penicillin-Binding Proteins; D010405:Penicillinase / Q000737:chemistry; D010406:Penicillins / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D001618:beta-Lactamases / Q000737:chemistry / Q000145:classification
D001426:Bacterial Proteins; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010406:Penicillins; D010405:Penicillinase; D001618:beta-Lactamases