III - Functional and phylogenetic studies of ABC systems
(Dorothée Murat, Laurent Goncalves and Elie Dassa)
The ATP-Binding Cassette (ABC) systems constitute the largest family of paralogues ever found. They are involved in a variety of biological processes, including not only transport across membranes, but also regulation of translation and transcription or DNA repair. In humans, 15 severe inherited diseases (including cystic fibrosis) are caused by the dysfunction of ABC transporters.
1) Functional study: orphans ABC proteins
Number of ABC proteins have no identified membrane associated partners. Several functions have been characterized and deal with transcription or translation regulation and DNA repair. In Staphylococcus aureus, the Vga protein is involved in streptogramin resistance. A collaboration with O. Chesneau was undertaken to understand the resistance mechanism. Four Escherichia coli genes with unknown functions belong to the same family and are investigated (D. Murat, A. Pak, J. Mahaux L. Goncalves et E. Dassa). The Programme Tranversal de Recherches N°131 of the Pasteur Institute (co-ordinated by E. Dassa) investigates the consequences on inactivation of homologous ORFs in the genomes of Salmonella typhimurium, S. aureus, Helicobacter pylori, Vibrio cholerae and Synechocystis.
2) Phylogenetic study: evolution of ABC systems
We developped a comprehensive database (ABCISSE) on these systems gathering sequences, structures and functions . More than 2650 different ABC ATPases and over 7000 ABC-related genes (taking their partners into account) are registered. An automated annotation tool allows to predict the functions (rarely investigated experimentally, and unknown in half of the cases), the substrate specificities and the ATPases partners.
Our phylogenetic analysis clusters ABC systems in three classes which match perfectly with the three functional classes : importers (exclusively prokaryotic), exporters and ABC systems apparently devoid of transmembrane domains probably involved in regulatory processes. The analysis of ABC systems in fully sequenced eukaryotic genomes suggests that eukaryotes use a relatively limited set of essential ABC systems, irrespectively of very large differences in genome sizes. We identified 6 typical prokaryote systems in the nuclear genome of Arabidopsis : most of eukaryotic ABC systems were probably acquired from the symbiotic bacterial ancestors of mitochondria and chloroplasts (E. Dassa, A. Charlery, O. Garcia, P. Bouige).
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