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

Title: The Staphylococcus aureus pSK41 plasmid-encoded ArtA protein is a master regulator of plasmid transmission genes and contains a RHH motif used in alternate DNA-binding modes

Journal Article · · Nucleic Acids Research
DOI:https://doi.org/10.1093/nar/gkp756· OSTI ID:1625466
 [1];  [2];  [1];  [2];  [2];  [2];  [3];  [2];  [2];  [1]
  1. University of Texas, Houston, TX (United States)
  2. University of Sydney, NSW (Australia)
  3. Flinders University, Adelaide, SA (Australia)
+ Show Author Affiliations

Plasmids harbored by Staphylococcus aureus are a major contributor to the spread of bacterial multi-drug resistance. Plasmid conjugation and partition are critical to the dissemination and inheritance of such plasmids. Here, we demonstrate that the ArtA protein encoded by the S. aureus multi-resistance plasmid pSK41 is a global transcriptional regulator of pSK41 genes, including those involved in conjugation and segregation. ArtA shows no sequence homology to any structurally characterized DNA-binding protein. To elucidate the mechanism by which it specifically recognizes its DNA site, we obtained the structure of ArtA bound to its cognate operator, ACATGACATG. The structure reveals that ArtA is representative of a new family of ribbon–helix–helix (RHH) DNA-binding proteins that contain extended, N-terminal basic motifs. Strikingly, unlike most well-studied RHH proteins ArtA binds its cognate operators as a dimer. However, we demonstrate that it is also able to recognize an atypical operator site by binding as a dimer-of-dimers and the extended N-terminal regions of ArtA were shown to be essential for this dimer-of-dimer binding mode. Thus, these data indicate that ArtA is a master regulator of genes critical for both horizontal and vertical transmission of pSK41 and that it can recognize DNA utilizing alternate binding modes.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES). Materials Sciences & Engineering Division
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1625466
Journal Information:
Nucleic Acids Research, Vol. 37, Issue 20; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English

References (50)

Methicillin-Resistant Staphylococcus aureus : A Public Health Issue with Economic Consequences
  • Goetghebeur, Mireille; Landry, Pierre-Alexandre; Han, Donald
  • Canadian Journal of Infectious Diseases and Medical Microbiology, Vol. 18, Issue 1 https://doi.org/10.1155/2007/253947
journal January 2007
IS257-mediated cointegration in the evolution of a family of staphylococcal trimethoprim resistance plasmids. journal January 1996
Transcriptional regulation by TrsN of conjugative transfer genes on staphylococcal plasmid pGO1. journal January 1994
A multimer resolution system contributes to segregational stability of the prototypical staphylococcal conjugative multiresistance plasmid pSK41 journal July 2008
Crystallography & NMR System: A New Software Suite for Macromolecular Structure Determination journal September 1998
Methicillin-resistant Staphylococcus aureus control in the 21st century: beyond the acute care hospital journal January 2008
Plasmid transcriptional repressor CopG oligomerises to render helical superstructures unbound and in complexes with oligonucleotides journal July 2001
A rapid alkaline extraction procedure for screening recombinant plasmid DNA journal January 1979
Improved methods for building protein models in electron density maps and the location of errors in these models journal March 1991
Analysis of the pSK1 replicon, a prototype from the staphylococcal multiresistance plasmid family journal October 2008
Structure of the Bacterial RNA Polymerase Promoter Specificity σ Subunit journal March 2002
Competition and Coadsorption of Di-acids and Carboxylic Acid Solvents on HOPG journal September 2006
Staphylococcus aureus multiresistance plasmid pSK41: analysis of the replication region, initiator protein binding and antisense RNA regulation: Replication of plasmid pSK41 journal January 2004
Structural Basis of the Transcriptional Regulation of the Proline Utilization Regulon by Multifunctional PutA journal August 2008
Conformational and Helicoidal Analysis of 30 PS of Molecular Dynamics on the d(CGCGAATTCGCG) Double Helix: “Curves”, Dials and Windows journal February 1989
The F plasmid traY gene product binds DNA as a monomer or a dimer: structural and functional implications journal June 1996
Molecular systematic studies of eubacteria, using sigma70-type sigma factors of group 1 and group 2. journal March 1997
The molecular evolution of methicillin-resistant Staphylococcus aureus journal March 2007
DNA recognition by β-sheets in the Arc represser–operator crystal structure journal February 1994
Analysis of a transfer region from the staphylococcal conjugative plasmid pSK41 journal December 1993
Structures of   repressors bound to direct and inverted DNA repeats explain modulation of transcription journal March 2006
Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mpl8 and pUC19 vectors journal January 1985
The structure of plasmid-encoded transcriptional repressor CopG unliganded and bound to its operator journal December 1998
Genetics: Accessory Elements and Genetic Exchange book April 2014
Coot model-building tools for molecular graphics journal November 2004
Identification and Characterization of the DNA-binding Domain of the Multifunctional PutA Flavoenzyme journal May 2004
The toxic shock syndrome exotoxin structural gene is not detectably transmitted by a prophage journal October 1983
Crystal structure of the met represser–operator complex at 2.8 Å resolution reveals DNA recognition by β-strands journal October 1992
Transcription regulatory circuits in bacterial plasmids journal October 2006
Improved method for electroporation of Staphylococcus aureus journal July 1992
Ribbon–helix–helix transcription factors: variations on a theme journal September 2007
Structure and Function of Bacterial Sigma Factors journal June 1988
DNA sequence and units of transcription of the conjugative transfer gene complex (trs) of Staphylococcus aureus plasmid pGO1. journal January 1993
Crystal structure of the nickel-responsive transcription factor NikR journal September 2003
Characterization of a Novel Partition System Encoded by the δ and ω Genes from the Streptococcal Plasmid pSM19035 journal June 2006
Segrosome structure revealed by a complex of ParR with centromere DNA journal December 2007
Multicopy expression vectors carrying the lac represser gene for regulated high-level expression of genes in Escherichia coli journal January 1987
Automated MAD and MIR structure solution journal April 1999
Biochemical and genetic analysis of operator contacts made by residues within the beta-sheet DNA binding motif of Mnt repressor. journal January 1992
Characterization of the stacking interactions between DNA or RNA nucleobases and the aromatic amino acids journal August 2007
Corrected nucleotide sequence of M13mp18 gene III journal May 1992
Overcrowding and understaffing in modern health-care systems: key determinants in meticillin-resistant Staphylococcus aureus transmission journal July 2008
Probing met represser–operator recognition in solution journal October 1992
Structure of FitAB from Neisseria gonorrhoeae Bound to DNA Reveals a Tetramer of Toxin-Antitoxin Heterodimers Containing Pin Domains and Ribbon-Helix-Helix Motifs journal December 2006
Replication Control of Staphylococcal Multiresistance Plasmid pSK41: an Antisense RNA Mediates Dual-Level Regulation of Rep Expression journal June 2006
Complete Nucleotide Sequence of pSK41: Evolution of Staphylococcal Conjugative Multiresistance Plasmids journal September 1998
An IS257-Derived Hybrid Promoter Directs Transcription of a tetA(K) Tetracycline Resistance Gene in theStaphylococcus aureus Chromosomal mecRegion journal June 2000
Replication of Staphylococcal Multiresistance Plasmids journal April 2000
Nature and Interactions of the Genetic Elements Governing Penicillinase Synthesis in Staphylococcus aureus journal January 1965
Fluorescence polarization analysis of protein-DNA and protein-protein interactions. journal June 1996

Cited By (8)

Perivascular macrophages mediate neutrophil recruitment during bacterial skin infection journal November 2013
Segrosome assembly at the pliable parH centromere journal March 2011
Crystal structure and centromere binding of the plasmid segregation protein ParB from pCXC100 journal December 2010
AmrZ Beta-Sheet Residues Are Essential for DNA Binding and Transcriptional Control of Pseudomonas aeruginosa Virulence Genes journal October 2010
Regulation of Gram-Positive Conjugation journal May 2019
The Transcription Factor AmrZ Utilizes Multiple DNA Binding Modes to Recognize Activator and Repressor Sequences of Pseudomonas aeruginosa Virulence Genes journal April 2012
Combinatorial targeting of ribbon–helix–helix artificial transcription factors to chimeric recognition sites journal April 2012
Dynamic Filament Formation by a Divergent Bacterial Actin-Like ParM Protein journal June 2016

Similar Records

Structure of the MecI repressor from Staphylococcus aureus in complex with the cognate DNA operator of mec
Journal Article · Sat Apr 01 00:00:00 EST 2006 · Acta Crystallographica. Section F · OSTI ID:1625466
+2 more
Structure of the Mecl Repressor from Staphylococcus aureus in Complex with the Cognate DNA Operator of mec
Journal Article · Sun Jan 01 00:00:00 EST 2006 · Acta Cryst. F · OSTI ID:1625466
+3 more
Processing of Nonconjugative Resistance Plasmids by Conjugation Nicking Enzyme of Staphylococci
Journal Article · Mon Jan 04 00:00:00 EST 2016 · Journal of Bacteriology · OSTI ID:1625466
+7 more

Related Subjects

59 BASIC BIOLOGICAL SCIENCES