University of Dundee

Transport of proteins by the bacterial Tat pathway

The Tat protein transport system functions to export folded proteins across the bacterial cytoplasmic membrane. Many Tat substrate proteins bind complex metal cofactors and the Tat pathway is required for important bacterial cellular processes including respiratory energy metabolism, photosynthesis, cell division, motility, quorum sensing, heavy metal resistance, iron and phosphate acquisition. The Tat system is found in many animal and plant bacterial pathogens where in most cases it is required for virulence [1].

The Tat system carries out a particularly challenging function as it must provide a passageway that allows transport of proteins from 30 Å - 60Å in diameter while at the same time ensuring that the membrane remains impermeable to protons and other ions. The Tat machinery shares no structural or sequence similarity with any other transport system and appears to operate by a distinct and unique mechanism [1].

Proteins are targeted to the Tat system by N-terminal signal peptides that contain a conserved twin arginine motif. Our studies with the model organism Escherichia coli have shown that the integral membrane proteins TatA, TatB, and TatC form essential components of the transport machinery. Multiple copies of TatB and TatC associate to form a large TatBC complex that recognises twin-arginine signal peptides and binds substrate proteins. Binding of substrate proteins to TatBC triggers polymerization of TatA to form the transmembrane translocation pathway [1].

Recently the crystal structure of the TatC component from Aquifex aeolicus has been determined. TatC contains six closely-packed transmembrane helices forming a central cavity on one face of the protein overhung by an extensive periplasmic cap [2]. This structure forms a framework for understanding the location and dynamic nature of the binding sites for the TatA and TatB partner proteins and the twin-arginine signal peptide [3]. The offered PhD project will use a combination of molecular biology, suppression genetics and cross-linking studies to explore the molecular interactions between the Tat components and the interactions with substrate proteins at different stages of the Tat traslocation cycle.

1.        Palmer, T. and Berks, B.C. Nature Reviews Microbiology 2012, 10, 483-496.

2.        Rollauer, S.E., et al. Nature 2012, 492, 210-214.

3.        Cleon, F. et al. Molecular Microbiology 2015, 98, 111-129.