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  Genmol


  Director : Anthony P. Pugsley (max@pasteur.fr)


  abstract

 

The Molecular Genetics Unit aims at achieving a greater understanding of basic molecular processes in well-characterized and readily amenable bacterial model systems. The unit is currently engaged in four major projects concerned with transcription activation and protein traffic.



  report

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Transcription activation by MalT protein in Escherichia coli (Group leader : Evelyne Richet) : MalT protein the transcription activator of operons encoding proteins involved in maltodextrin uptake and catabolism in the Enterobacteriaceae, is the prototype of a new family of bacterial regulatory proteins. Unusually for such proteins, MalT activity is tightly controlled by four ligands: a positive effector (maltotriose) and three negative effector proteins (Aes, MalY and MalK). Furthermore, MalT activity is controlled by the binding and hydrolysis of ATP. We are interested in the ways these signals are integrated by MalT. Structural analysis of the four domains of MalT is under way. Several lines of evidence converge to suggest that the three amino-terminal domains constitute a new signal integration module.

Protein secretion by the secreton (Group leader Anthony Pugsley) : The secreton is a complex machinery that recognizes and transports specific proteins from the periplasm into the growth medium. Secretion is energy-dependent and involves recognition of folded substrate proteins and, apparently, their transport through a large, multimeric gated channel (the secretin) in the outer membrane. Biochemical and structural studies of components of the machinery are beginning to reveal information on their organization and function. In addition, studies are underway to determine how the genes coding for the secreton, notably the E. coli chromosomal genes required for chitinase secretion, are regulated.

Type IV pilus assembly (Group leader Anthony Pugsley). The secreton genes are highly homologous to genes involved in type IV pilus biogenesis in many pathogenic Gram-negative bacteria. These genes include five coding for proteins whose products are reminiscent of pilins, the type IV pilus subunits (notably the highly-conserved N-terminal hydrophobic domain). Indeed, one of the pilin-like secreton components can be assembled into pili in bacteria expressing the secreton genes. This observation raises important questions concerning the real function of the secretion genes (secretion or pilus biogenesis), and the role of pili in secretion (as an element in the control of channel gating, as a motor or conduit to propel proteins beyond the cell surface or as an adhesin to anchor bacteria to substrates degraded by secreted enzymes).

Lipoprotein biogenesis and assembly (Group leader : Anthony Pugsley). Pullulanase, a protein secreted by the type II secreton, and one of the components of the secretin complex (see above) are both fatty acylated at their N-terminus. We have recently initiated a project on how lipoproteins are synthesized and sorted to their correct compartment. Our studies have refined the information on the sorting signal that directs a subclass of E. coli lipoproteins to the outer membrane and we have recently identified a protein that reaches this membrane despite lacking the appropriate sorting signal. Studies currently under way should provide molecular tools with which to study how lipoproteins are specifically localized to the inner membrane in E. coli.



  web site

puce More informations on our web site


  publications

puce Publications of the unit on Pasteur's references database


  personnel

  Office staff Researchers Scientific trainees Other personnel
 

Armelle Lavenir, Secretary, alavenir@pasteur.fr

Evelyne Richet, CNRS, Research Director,erichet@pasteur.fr

Olivier Danot, Institut Pasteur, Staff Scientist, olivdano@pasteur.fr

Olivera Francetic, Institut Pasteur, Staff Scientist, ofrancet@pasteur.fr

Odile Mary-Possot, Institut Pasteur, Staff Scientist, opossot@pasteur.fr

Nicolas Bayan, University of Paris XI, Assistant Professor, nbayan@pasteur.fr

Rolf Koehler, postdoc EC, rkoehler@pasteur.fr

Guillaume Vignon, PhD student, gvignon@pasteur.fr

Carine Robichon, PhD student, crobicho@pasteur.fr

Nicolas Joly, PhD student, jolyn@pasteur.fr

Dominique Vidal-Ingigliardi, Engineer, dvidalin@pasteur.fr

Ingrid Guilvout, Senior Technician, ingvout@pasteur.fr

Nathalie Nadeau, Technician, nnadeau@pasteur.fr Maria Reyngoud, Laboratory Assistant


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