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

Nucleic Acids Research
Stephen B CarrC D Thomas

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.

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Citations

Aug 5, 2016·Nucleic Acids Research·Cesar L PastranaFernando Moreno-Herrero
Oct 7, 2016·Frontiers in Molecular Biosciences·José A Ruiz-MasóGloria Del Solar
Dec 9, 2017·Frontiers in Microbiology·Stephen M KwongNeville Firth
Dec 19, 2017·Frontiers in Microbiology·Paweł WawrzyniakDariusz Bartosik
Jan 21, 2018·Scientific Reports·Algirdas ToleikisJustin E Molloy
Jan 14, 2020·Nucleic Acids Research·Carolina CarrascoFernando Moreno-Herrero
Jul 25, 2019·Nature Microbiology·Simon RouxEmiley A Eloe-Fadrosh
Aug 21, 2018·Bioscience, Biotechnology, and Biochemistry·Shuhei Hashiro, Hisashi Yasueda
Jul 18, 2021·Science Advances·Xiao YiMichael Travisano
Nov 17, 2021·Molecular Microbiology·István NagyJános Kiss
Dec 9, 2021·Microbiology and Molecular Biology Reviews : MMBR·M Pilar Garcillán-BarciaManuel Espinosa

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