University of Dundee

Inter-university research collaboration takes a big leap towards understanding the transport of folded proteins.

14 Dec 2012

The movement of proteins across biological membranes is an essential feature of all cells. In bacteria proteins can either be moved in an unfolded or a folded state. Unfolded proteins are much easier to transport because they require only a narrow channel that is not much wider than the diameter of an amino acid. However, not all proteins can be exported in an unfolded state, for example because they may need a non-covalently bound cofactor for activity, which they acquire in the cytoplasmic compartment. Whilst we know a great deal about how unfolded proteins are moved, much less is known about the movement of folded proteins.

Now, a collaboration between scientists in Oxford, Stockholm and Dundee has made a big leap forward in our understanding of this process by reporting the crystal structure of the membrane protein TatC. The Tat machinery is made up of three membrane proteins, TatA, B and C, which collectively move large folded proteins of variable diameters across the cell membrane. TatC along with its TatB partner protein form a complex that binds Tat substrate proteins whilst TatA is believed to form a size-variable transport channel. TatC is the major organising component of the Tat machinery because it contains the binding site for substrate proteins and it recruits TatA to assemble the transport channel. This structure therefore provides a framework for understanding the unique Tat transport mechanism.

Professor Tracy Palmer of the Division of Molecular Microbiology at the College of Life Sciences in Dundee said “Collectively we have made a big step forward in our long term goal of understanding how this fascinating secretion machine operates at a molecular level. This will not just satisfy our scientific curiosity, but might ultimately pave the way for the development of antibiotic compounds that block the machinery in pathogenic bacteria. A detailed understanding of the Tat machinery also offers the potential to exploit the system to secrete proteins of pharmaceutical and industrial importance.”

The findings are published in Nature this week:

Structure of the TatC core of the twin-arginine protein transport system Nature492,210–214(13 December 2012)

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