An integrative approach to the study of filamentous oligomeric assemblies, with application to RecA

PLoS One. 2015 Mar 18;10(3):e0116414. doi: 10.1371/journal.pone.0116414. eCollection 2015.

Abstract

Oligomeric macromolecules in the cell self-organize into a wide variety of geometrical motifs such as helices, rings or linear filaments. The recombinase proteins involved in homologous recombination present many such assembly motifs. Here, we examine in particular the polymorphic characteristics of RecA, the most studied member of the recombinase family, using an integrative approach that relates local modes of monomer/monomer association to the global architecture of their screw-type organization. In our approach, local modes of association are sampled via docking or Monte Carlo simulations. This enables shedding new light on fiber morphologies that may be adopted by the RecA protein. Two distinct RecA helical morphologies, the so-called "extended" and "compressed" forms, are known to play a role in homologous recombination. We investigate the variability within each form in terms of helical parameters and steric accessibility. We also address possible helical discontinuities in RecA filaments due to multiple monomer-monomer association modes. By relating local interface organization to global filament morphology, the strategies developed here to study RecA self-assembly are particularly well suited to other DNA-binding proteins and to filamentous protein assemblies in general.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Models, Molecular*
  • Protein Structure, Quaternary
  • Rec A Recombinases / chemistry*

Substances

  • Rec A Recombinases

Grant support

The authors acknowledge support from Université Paris 6 (to B.B.), the French CNRS (Centre National de la Recherche Scientifique, to J.E.), IFCPAR (Indo-French Center for the Promotion of Advanced Research, to C.H.R.), the German DFG (Deutsche Forschungsgemeinschaft, within SFB749, project C5, to M.Z.), and the “Initiative d’Excellence” program from the French State (Grant “DYNAMO”, ANR-11-LABX-0011-01, to C.P. and C.H.R.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.