Bacterial
Membranes
Unit
Institut Pasteur
25 Rue du Docteur Roux
75724 Paris Cedex 15
FRANCE
Tel: 33 (0)1 45 68 88 16
Fax : 33 (0)1 45 68 87 90
Secretary:
Mme Sylvana Thépaut
sthepaut@pasteur
     
   
   
 

II - Protein secretion by Gram negative ABC transporters
(Sandra Cescau, Annick Paquelin et Philippe Delepelaire)

Four secretion pathways have been actually described in Gram-negative bacteria. Type II pathway requires the universal N-terminal signal peptide and the general export pathway (Sec system) to the cross of the inner membrane. Type I and III pathways are independent of the signal peptide and Sec system.
The Type I secretion pathway also called the ABC secretion pathway consists of three proteins located in the cell envelope: the ABC protein belonging to the ATP Binding Cassette class of proteins, another cytoplasmic membrane protein and an outer membrane component.
ATP Binding Cassette (ABC) transporters are implicated in the vectorial movement of solutes across biological membranes. They constitute one of the most abundant family of proteins in the living organisms where they play essential functions as evidenced by the growing number of human health disorders linked to an ABC transporter defect. ABC proteins are also involved in drug efflux in eukaryotes and prokaryotes.
Our work has largely contributed to show that bacterial ABC protein exporters are widespread in Gram-negative organisms. We have shown that in several cases (such as the E. coli hemolysin transporter) the outer membrane component belongs to the TolC family and is a multifunctional protein involved in drug efflux and colicin import. All the proteins following this pathway, including the hemophore, have a C-terminal secretion signal. Binding of this signal to the ABC protein modulates its ATPase activity and triggers the association of the three secretion proteins in a multiprotein complex. The C-terminal signal remains accessible owing to cytoplasmic chaperones which are required for secretion. In the case of the hemophore, SecB is the chaperone that keeps HasA in secretion competent state. In absence of the transporter or SecB, HasA accumulates in the cytoplasm in a folded form that is unable to be secreted but nevertheless still able to interact with the transporter. The ABC protein has several interaction sites with its substrate that we are currently trying to characterize. Determination of these domains could help to design new drugs able to inhibit ABC proteins involved in multidrug resistance.

Our current researchs are divided in two objectives: one is chaperone role and conformationnal state of substrate compatible with secretion. The second is the dynamic association of the transporteur in a multiproteins complex. We are presently purifying the ABC transporter multiprotein complex to study it by crystallography and cryomicroscopy. This is done in collaboration with the laboratory of Electronic Microscopy of the Institut Pasteur and abroad with R.M. Glaeser, Lawrence Berkeley National Laboratory, California University, Berkeley USA.


L'appareil de sécrétion de l'hémophore

Le systËme de sÈcrÈtion ABC


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