skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Journal Article · · Nature Structural & Molecular Biology
DOI:https://doi.org/10.1038/nsmb.3286· OSTI ID:1347024
 [1];  [1];  [2];  [1];  [3];  [1]
  1. Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology
  2. Univ. of Chicago, IL (United States). Dept. of Biochemistry and Molecular Biology; Abbott Lab., North Chicago, IL (United States)
  3. Univ. of Chicago, IL (United States). Dept. of Pediatrics; Univ. of Chicago, IL (United States). MRSA Research Center

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.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Organization:
USDOE Office of Science (SC); National Institutes of Health (NIH)
DOE Contract Number:
R21AI117593
OSTI ID:
1347024
Journal Information:
Nature Structural & Molecular Biology, Vol. 23, Issue 10; ISSN 1545-9993
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH

References (26)

CDD: NCBI's conserved domain database journal November 2014
MRSA: the first half century journal October 2011
Structure of the eukaryotic replicative CMG helicase suggests a pumpjack motion for translocation journal February 2016
Geneious Basic: An integrated and extendable desktop software platform for the organization and analysis of sequence data journal April 2012
DNA stretching by bacterial initiators promotes replication origin opening journal October 2011
Crystal structure of the eukaryotic origin recognition complex journal March 2015
Structure and mechanism of the RuvB holliday junction branch migration motor journal August 2001
The phage-related chromosomal islands of Gram-positive bacteria journal August 2010
Replication Origin Recognition and Deformation by a Heterodimeric Archaeal Orc1 Complex journal August 2007
Loading and activation of DNA replicative helicases: the key step of initiation of DNA replication journal March 2013
Crystal Structure of T7 Gene 4 Ring Helicase Indicates a Mechanism for Sequential Hydrolysis of Nucleotides journal June 2000
Features and development of Coot journal March 2010
Mechanisms of Site-Specific Recombination journal June 2006
PHENIX: a comprehensive Python-based system for macromolecular structure solution journal January 2010
Evolutionary Relationships and Structural Mechanisms of aaa+ Proteins journal June 2006
Gapped BLAST and PSI-BLAST: a new generation of protein database search programs journal September 1997
Mechanism of DNA translocation in a replicative hexameric helicase journal July 2006
Dali: a network tool for protein structure comparison journal November 1995
Protein structure prediction on the Web: a case study using the Phyre server journal February 2009
Community-Associated Methicillin-Resistant Staphylococcus aureus: Epidemiology and Clinical Consequences of an Emerging Epidemic journal July 2010
Structure of the eukaryotic MCM complex at 3.8 Å journal July 2015
Roles of two large serine recombinases in mobilizing the methicillin-resistance cassette SCC mec: Roles of the SCCmec recombinases journal May 2013
A New Class of Genetic Element, Staphylococcus Cassette Chromosome mec, Encodes Methicillin Resistance in Staphylococcus aureus journal June 2000
Blue native PAGE journal June 2006
Evolutionary history and higher order classification of AAA+ ATPases journal April 2004
[20] Processing of X-ray diffraction data collected in oscillation mode book January 1997