5MBV

Cryo-EM structure of Lambda Phage protein GamS bound to RecBCD.

Summary for 5MBV

• Entry DOI: 10.2210/pdb5mbv/pdb
• Related: 5ld2
• EMDB information: 3460
• Descriptor: RecBCD enzyme subunit RecB, RecBCD enzyme subunit RecC, RecBCD enzyme subunit RecD, ... (4 entities in total)
• Functional Keywords: inhibitor, complex, dna repair, helicase/nuclease, dna binding protein
• Biological source: Escherichia coli; More
• Total number of polymer chains: 5
• Total formula weight: 353513.08

Authors

Wilkinson, M.,Chaban, Y.,Wigley, D.B. (deposition date: 2016-11-08, release date: 2017-01-11, Last modification date: 2024-05-15)

Primary citation

Wilkinson, M.,Troman, L.,Wan Nur Ismah, W.A.,Chaban, Y.,Avison, M.B.,Dillingham, M.S.,Wigley, D.B.
Structural basis for the inhibition of RecBCD by Gam and its synergistic antibacterial effect with quinolones.
Elife, 5:-, 2016

PubMed Abstract: Our previous paper (Wilkinson , 2016) used high-resolution cryo-electron microscopy to solve the structure of the RecBCD complex, which acts in both the repair of double-stranded DNA breaks and the degradation of bacteriophage DNA. To counteract the latter activity, bacteriophage λ encodes a small protein inhibitor called Gam that binds to RecBCD and inactivates the complex. Here, we show that Gam inhibits RecBCD by competing at the DNA-binding site. The interaction surface is extensive and involves molecular mimicry of the DNA substrate. We also show that expression of Gam in or increases sensitivity to fluoroquinolones; antibacterials that kill cells by inhibiting topoisomerases and inducing double-stranded DNA breaks. Furthermore, fluoroquinolone-resistance in clinical isolates is reversed by expression of Gam. Together, our data explain the synthetic lethality observed between topoisomerase-induced DNA breaks and the RecBCD gene products, suggesting a new co-antibacterial strategy.

PubMed: 28009252
DOI: 10.7554/eLife.22963

Experimental method

ELECTRON MICROSCOPY (3.8 Å)