Structure-function analysis of pneumococcal DprA protein reveals that dimerization is crucial for loading RecA recombinase onto DNA during transformation

Sophie Quevillon-Cheruel, Nathalie Campo, Nicolas Mirouze, Isabelle Mortier-Barriere, Mark A Brooks, Marion Boudes, Dominique Durand, Anne-Lise Soulet, Johnny Lisboa, Phillippe Noirot, Bernard Martin, Herman van Tilbeurgh, Marie-Francoise Noirot-Gros, Jean-Pierre Claverys, Patrice Polard

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48 Citations (Scopus)


Transformation promotes genome plasticity in bacteria via RecA-driven homologous recombination. In the Gram-positive human pathogen Streptococcus pneumoniae, the transformasome a multiprotein complex, internalizes, protects, and processes transforming DNA to generate chromosomal recombinants. Double-stranded DNA is internalized as single strands, onto which the transformation-dedicated DNA processing protein A (DprA) ensures the loading of RecA to form presynaptic filaments. We report that the structure of DprA consists of the association of a sterile alpha motif domain and a Rossmann fold and that DprA forms tail-to-tail dimers. The isolation of DprA self-interaction mutants revealed that dimerization is crucial for the formation of nucleocomplexes in vitro and for genetic transformation. Residues important for DprA-RecA interaction also were identified and mutated, establishing this interaction as equally important for transformation. Positioning of key interaction residues on the DprA structure revealed an overlap of DprA-DprA and DprA-RecA interaction surfaces. We propose a model in which RecA interaction promotes rearrangement or disruption of the DprA dimer, enabling the subsequent nucleation of RecA and its polymerization onto ssDNA.
Original languageEnglish
Pages (from-to)E2466 - E2475
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number37
Publication statusPublished - 2012
Externally publishedYes

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