Referencia

The structure of a polygamous repressor reveals how phage-inducible chromosomal islands spread in nature.
Ciges-Tomas JR*, Alite C*, Humphrey S*, Donderis J, Bowring J, Salvatella X, Penadés JR, Marina A.
Nature Communications. 2019 Aug 15;10(1):3676. doi: 10.1038/s41467-019-11504-2.nature comm

Autores

Ciges-Tomas JR*, Alite C*, Humphrey S*, Donderis J, Bowring J, Salvatella X, Penadés JR, Marina A.

Resumen

Stl is a master repressor encoded by Staphylococcus aureus pathogenicity islands (SaPIs) that maintains integration of these elements in the bacterial chromosome. After infection or induction of a resident helper phage, SaPIs are de-repressed by specific interactions of phage proteins with Stl. SaPIs have evolved a fascinating mechanism to ensure their promiscuous transfer by targeting structurally unrelated proteins performing identically conserved functions for the phage. Here we decipher the molecular mechanism of this elegant strategy by determining the structure of SaPIbov1 Stl alone and in complex with two structurally unrelated dUTPases from different S. aureus phages. Remarkably, SaPIbov1 Stl has evolved different domains implicated in DNA and partner recognition specificity. This work presents the solved structure of a SaPI repressor protein and the discovery of a modular repressor that acquires multispecificity through domain recruiting. Our results establish the mechanism that allows widespread dissemination of SaPIs in nature.

Descripción

Las islas de patogenicidad son elementos genéticos que movilizan toxinas y otros factores de virulencia. Las islas se encuentran de forma quiescente en el genoma del hospedador bajo el control del represor Stl esperando a ser inducidas por fagos a los que parasitan. A través de una aproximación estructural hemos mostrado que Stl es un novedoso tipo de represor multimodular que ha reclutado dominios especializados para reconocer proteínas no estructuralmente relacionas aunque si funcionalmente de los fagos inductores de islas. Esta estrategia permite a la isla una fina regulación del ciclo a la vez que evita la evasión del fago por mutación de la proteína inductora, asegurando así su eficiente transferencia y diseminación en la naturaleza.

 

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REFERENCIA DEL GRUPO INVESTIGADOR

La Unidad de Cristalografía de Macromoléculas del Instituto de Biomedicina de Valencia-CSIC es un grupo de investigación del Consejo Superior de Investigaciones Científicas y CIBERER liderado por el Dr. Alberto Marina Moreno. El grupo estudia los mecanismos moleculares de señalización y comunicación en el mundo microbiano. Para ello el grupo emplea una aproximación principalmente bioquímica y biofísica, destacando entre las últimas la cristalografía de rayos X.

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