4PQK: C-Terminal domain of DNA binding protein

The staphylococcal multiresistance plasmids are key contributors to the alarming rise in bacterial multidrug resistance. A conserved replication initiator, RepA, encoded on these plasmids is essential for their propagation. RepA proteins consist of flexibly linked N-terminal (NTD) and C-terminal (CTD) domains. Despite their essential role in replication, the molecular basis for RepA function is unknown. Here we describe a complete structural and functional dissection of RepA proteins. Unexpectedly, both the RepA NTD and CTD show similarity to the corresponding domains of the bacterial primosome protein, DnaD. Although the RepA and DnaD NTD both contain winged helix-turn-helices, the DnaD NTD self-assembles into large scaffolds whereas the tetrameric RepA NTD binds DNA iterons using a newly described DNA binding mode. Strikingly, structural and atomic force microscopy data reveal that the NTD tetramer mediates DNA bridging, suggesting a molecular mechanism for origin handcuffing. Finally, data show that the RepA CTD interacts with the host DnaG primase, which binds the replicative helicase. Thus, these combined data reveal the molecular mechanism by which RepA mediates the specific replicon assembly of staphylococcal multiresistant plasmids.
PDB ID: 4PQKDownload
MMDB ID: 120859
PDB Deposition Date: 2014/3/3
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 3.401  Å
Source Organism:
Similar Structures:
Biological Unit for 4PQK: monomeric; determined by author and by software (PISA)
Molecular Components in 4PQK
Label Count Molecule
Protein (1 molecule)
Maltose ABC Transporter Periplasmic Protein, Truncated Replication Protein Repa
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB