Protein translocation and membrane protein insertion are essential processes for the biogenesis of any living cell. In bacteria, the main route for protein secretion and membrane protein insertion is formed by the Sec-pathway. This system consists of the translocase, a multi-subunit protein complex. Its core is formed by a universally conserved trimeric integral membrane complex SecYEG which constitutes the protein-conducting channel, and the SecA protein which functions as an ATP-driven motor protein. SecA drives the stepwise translocation of pre-proteins across the membrane through multiple cycles of ATP binding and hydrolysis. The integral membrane proteins SecD, SecF and YajC form a sub-complex that associates with SecYEG and that add to the fidelity of protein secretion. YidC is a member of the conserved Alb3/Oxa1/YidC family, and contacts hydrophobic anchor sequences of membrane proteins during their insertion into the membrane. Whereas many secretory proteins are targeted to the translocase via the molecular chaperone SecB, membrane proteins mostly utilize a co-translational targeting route which involves bacterial homologs of the eukaryotic signal recognition particle and its membrane receptor.
Our aim is to elucidate the mechanism of preprotein translocation and the insertion of membrane protein complexes into the lipid bilayer. In both processes,we relate the structure of the translocase to its function with a focus on the dynamics of the process and the conformational changes during the reaction. The Escherichia coli translocase is used as a model system.
Research is directed at:
- Macromechanics of protein unfolding during translocation and the role of SecA in this process
- Functional and structural analysis of the SecYEG complex
- Role of YidC in membrane protein insertion
For further reading and background information see:
Driessen, A.J.M., Nouwen, N. (2008) Protein translocation across the bacterial cytoplasmic membrane. Annu. Rev. Biochem . 77 :643-67.
Mitra, K., Frank, J., Driessen, A.J.M. (2006) Co- and Post-translational Translocation through the Protein-conducting Channel: Analogous Mechanisms at Work? Nat. Struc. Mol. Biol. 13: 959-966 .
Van der Laan, M. Nouwen, N.P., Driessen, A.J.M. (2005) YidC – an Evolutionary Conserved Device for the Assembly of Energy-transducing Membrane Protein Complexes. Curr. Opinion Microbiol. 8: 182-187.
Driessen, A.J.M. (2005) Cell Biology: Two Pores Better Than One? Nature 438: 299-300.
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