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Structures of replication initiation proteins from staphylococcal antibiotic resistance plasmids reveal protein asymmetry and flexibility are necessary for replication

DOI: 10.1093/nar/gkv1539 DOI Help
PMID: 26792891 PMID Help

Authors: Stephen B. Carr (Research Complex at Harwell) , Simon E. V. Phillips (Research Complex at Harwell) , Christopher D. Thomas (University of Leeds)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nucleic Acids Research

State: Published (Approved)
Published: January 2016

Open Access Open Access

Abstract: Antibiotic resistance in pathogenic bacteria is a continual threat to human health, often residing in extrachromosomal plasmid DNA. Plasmids of the pT181 family are widespread and confer various antibiotic resistances to Staphylococcus aureus. They replicate via a rolling circle mechanism that requires a multi-functional, plasmid-encoded replication protein to initiate replication, recruit a helicase to the site of initiation and terminate replication after DNA synthesis is complete. We present the first atomic resolution structures of three such replication proteins that reveal distinct, functionally relevant conformations. The proteins possess a unique active site and have been shown to contain a catalytically essential metal ion that is bound in a manner distinct from that of any other rolling circle replication proteins. These structures are the first examples of the Rep_trans Pfam family providing insights into the replication of numerous antibiotic resistance plasmids from Gram-positive bacteria, Gram-negative phage and the mobilisation of DNA by conjugative transposons.

Journal Keywords: Staphylococcus aureus; Antibiotic resistance; Structural Biology

Subject Areas: Biology and Bio-materials


Instruments: I02-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography

Other Facilities: ESRF and Daresbury