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Section: Application Domains

Prokaryotic Type IV Secretion Systems

Participants : Marie-Dominique Devignes [contact person] , Isaure Chauvot de Beauchêne [contact person] , Bernard Maigret, David Ritchie, Philippe Noel, Antoine Moniot, Dominique Mias-Lucquin.

Concerning Axis 2 : "Integrative Multi-Component Assembly and Modeling", our first application domain is related to prokaryotic type IV secretion systems.

Prokaryotic type IV secretion systems constitute a fascinating example of a family of nanomachines capable of translocating DNA and protein molecules through the cell membrane from one cell to another [36]. The complete system involves at least 12 proteins. The structure of the core channel involving three of these proteins has recently been determined by cryo-EM experiments for Gram-negative bacteria [47], [63]. However, the detailed nature of the interactions between the other components and the core channel remains to be found. Therefore, these secretion systems represent a family of complex biological systems that call for integrated modeling approaches to fully understand their machinery.

In the framework of the Lorraine Université d'Excellence (LUE-FEDER) “CITRAM” project we are pursuing our collaboration with Nathalie Leblond of the Genome Dynamics and Microbial Adaptation (DynAMic) laboratory (UMR 1128, Université de Lorraine, INRA) on the mechanism of horizontal transfer by integrative conjugative elements (ICEs) and integrative mobilisable elements (IMEs) in prokaryotic genomes. These elements use Type IV secretion systems for transferring DNA horizontally from one cell to another. We have discovered more than 200 new ICEs/IMEs by systematic exploration of 72 Streptococcus genomes and characterized a new class of relaxases [21]. We have modeled the dimer of this relaxase protein by homology with a known structure. For this, we have created a new pipeline to model symmetrical dimers of multi-domains proteins. As one activity of the relaxase is to cut the DNA for its transfer, we are also currently studying the DNA-protein interactions that are involved in this very first step of horizontal transfer (see next section).