7B5G

Crystal structure of E.coli LexA in complex with nanobody NbSOS3(Nb14527)

Summary for 7B5G

• Entry DOI: 10.2210/pdb7b5g/pdb
• Descriptor: LexA repressor, Nanobody Nb14527, NbSOS3, 1,2-ETHANEDIOL, ... (4 entities in total)
• Functional Keywords: transcriptional repressor dna binding autoproteolysis nanobodies, transcription
• Biological source: Escherichia coli K-12; More
• Total number of polymer chains: 8
• Total formula weight: 147125.40

Authors

Maso, L.,Vascon, F.,Chinellato, M.,Pardon, E.,Steyaert, J.,Angelini, A.,Tondi, D.,Cendron, L. (deposition date: 2020-12-03, release date: 2022-09-14, Last modification date: 2024-11-13)

Primary citation

Maso, L.,Vascon, F.,Chinellato, M.,Goormaghtigh, F.,Bellio, P.,Campagnaro, E.,Van Melderen, L.,Ruzzene, M.,Pardon, E.,Angelini, A.,Celenza, G.,Steyaert, J.,Tondi, D.,Cendron, L.
Nanobodies targeting LexA autocleavage disclose a novel suppression strategy of SOS-response pathway.
Structure, 30:1479-, 2022

PubMed Abstract: Antimicrobial resistance threatens the eradication of infectious diseases and impairs the efficacy of available therapeutics. The bacterial SOS pathway is a conserved response triggered by genotoxic stresses and represents one of the principal mechanisms that lead to resistance. The RecA recombinase acts as a DNA-damage sensor inducing the autoproteolysis of the transcriptional repressor LexA, thereby derepressing SOS genes that mediate DNA repair, survival to chemotherapy, and hypermutation. The inhibition of such pathway represents a promising strategy for delaying the evolution of antimicrobial resistance. We report the identification, via llama immunization and phage display, of nanobodies that bind LexA with sub-micromolar affinity and block autoproteolysis, repressing SOS response in Escherichia coli. Biophysical characterization of nanobody-LexA complexes revealed that they act by trapping LexA in an inactive conformation and interfering with RecA engagement. Our studies pave the way to the development of new-generation antibiotic adjuvants for the treatment of bacterial infections.

PubMed: 36240773
DOI: 10.1016/j.str.2022.09.004

Experimental method

X-RAY DIFFRACTION (2.4 Å)