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Structural basis of a histidine-DNA nicking/joining mechanism for gene transfer and promiscuous spread of antibiotic resistance

Journal Article · · Proceedings of the National Academy of Sciences of the United States of America
 [1];  [2];  [3];  [4];  [5];  [3];  [6];  [7];  [3];  [6]
  1. Barcelona Institute of Science and Technology, Barcelona (Spain); Molecular Biology Institute of Barcelona, Barcelona (Spain); International Institute of Molecular and Cell Biology in Warsaw, Warsaw (Poland)
  2. Barcelona Institute of Science and Technology, Barcelona (Spain); Molecular Biology Institute of Barcelona, Barcelona (Spain); CELLS-ALBA Synchrotron Light Source, Cerdanyola del Valles (Spain)
  3. Consejo Superior de Investigaciones Cientificas, Madrid (Spain)
  4. Barcelona Institute of Science and Technology, Barcelona (Spain); Molecular Biology Institute of Barcelona, Barcelona (Spain); SLAC National Accelerator Lab., Menlo Park, CA (United States)
  5. Barcelona Institute of Science and Technology, Barcelona (Spain); Barcelona Institute of Science and Technology, Barcelona (Spain)
  6. Barcelona Institute of Science and Technology, Barcelona (Spain); Molecular Biology Institute of Barcelona, Barcelona (Spain)
  7. Barcelona Institute of Science and Technology, Barcelona (Spain); Barcelona Institute of Science and Technology, Barcelona (Spain); Univ. of Barcelona, Barcelona (Spain)
+ Show Author Affiliations
Relaxases are metal-dependent nucleases that break and join DNA for the initiation and completion of conjugative bacterial gene transfer. Conjugation is the main process through which antibiotic resistance spreads among bacteria, with multidrug-resistant staphylococci and streptococci infections posing major threats to human health. The MOBV family of relaxases accounts for approximately 85% of all relaxases found in Staphylococcus aureus isolates. Here, we present six structures of the MOBV relaxase MobM from the promiscuous plasmid pMV158 in complex with several origin of transfer DNA fragments. A combined structural, biochemical, and computational approach reveals that MobM follows a previously uncharacterized histidine/metal-dependent DNA processing mechanism, which involves the formation of a covalent phosphoramidate histidine-DNA adduct for cell-to-cell transfer. In conclusion, we discuss how the chemical features of the high-energy phosphorus-nitrogen bond shape the dominant position of MOBV histidine relaxases among small promiscuous plasmids and their preference toward Gram-positive bacteria.
Research Organization:
SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-76SF00515
OSTI ID:
1390289
Journal Information:
Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 32 Vol. 114; ISSN 0027-8424
Publisher:
National Academy of Sciences, Washington, DC (United States)Copyright Statement
Country of Publication:
United States
Language:
English

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Cited By (9)

Complete labelling of pneumococcal DNA-binding proteins with seleno-L-methionine journal November 2019
The Bacillus subtilis Conjugative Plasmid pLS20 Encodes Two Ribbon-Helix-Helix Type Auxiliary Relaxosome Proteins That Are Essential for Conjugation journal November 2017
Relaxase MobM Induces a Molecular Switch at Its Cognate Origin of Transfer journal February 2018
Computational and mutational analysis of TatD DNase of Bacillus anthracis journal February 2019
MOBscan: Automated Annotation of MOB Relaxases book October 2019
Suicide inactivation of the uracil DNA glycosylase UdgX by covalent complex formation journal May 2019
DNA processing by the MOBH family relaxase TraI encoded within the gonococcal genetic island journal July 2019
Characterization of a relaxase belonging to the MOBT family, a widespread family in Firmicutes mediating the transfer of ICEs journal May 2019
Regulation of Gram-Positive Conjugation journal May 2019

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Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
Staphylococcus aureus
X-ray structure
antibiotic resistance
histidine relaxase
horizontal gene transfer