Staphylococcal SCCmec elements encode an active MCM-like helicase and thus may be replicative

Nat Struct Mol Biol. 2016 Oct;23(10):891-898. doi: 10.1038/nsmb.3286. Epub 2016 Aug 29.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a public-health threat worldwide. Although the mobile genomic island responsible for this phenotype, staphylococcal cassette chromosome (SCC), has been thought to be nonreplicative, we predicted DNA-replication-related functions for some of the conserved proteins encoded by SCC. We show that one of these, Cch, is homologous to the self-loading initiator helicases of an unrelated family of genomic islands, that it is an active 3'-to-5' helicase and that the adjacent ORF encodes a single-stranded DNA-binding protein. Our 2.9-Å crystal structure of intact Cch shows that it forms a hexameric ring. Cch, like the archaeal and eukaryotic MCM-family replicative helicases, belongs to the pre-sensor II insert clade of AAA+ ATPases. Additionally, we found that SCC elements are part of a broader family of mobile elements, all of which encode a replication initiator upstream of their recombinases. Replication after excision would enhance the efficiency of horizontal gene transfer.

MeSH terms

  • Adenosine Triphosphatases / chemistry
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Chromosomes, Bacterial / genetics*
  • Crystallography, X-Ray
  • DNA Helicases / chemistry
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA Replication
  • DNA, Bacterial / genetics
  • DNA, Bacterial / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Methicillin-Resistant Staphylococcus aureus / chemistry
  • Methicillin-Resistant Staphylococcus aureus / genetics*
  • Methicillin-Resistant Staphylococcus aureus / metabolism
  • Models, Molecular
  • Open Reading Frames
  • Protein Conformation
  • Protein Domains
  • Protein Multimerization
  • Staphylococcal Infections / microbiology

Substances

  • Bacterial Proteins
  • DNA, Bacterial
  • DNA-Binding Proteins
  • Adenosine Triphosphatases
  • DNA Helicases