research advances
May 2009 featured article
You look familiar: the Type VI secretion system
PSI-SGKB [doi:10.1038/fa_psisgkb.2009.24]
New structures raise the perplexing question of which came first, the bacterial secretion system or the bacteriophage tail.
Many pathogenic bacteria secrete proteins across the bacterial cell membrane. At least six different multiprotein complexes are used to transport secreted proteins, and these are known as the Type I to Type VI secretion systems. The first five are reasonably well understood, but information on the most recently discovered, the Type VI secretion system, has been sparse. Two papers 1, 2 provide structures of several Type VI proteins and reveal the overall similarity of the complex to the tails of bacteriophages—via which the bacteriophage DNA is injected into its host. This is an excellent example of the power of structural studies to reveal function.
The Type VI secretion system was discovered in 2006 and consists of between 15 and 20 proteins. Early bioinformatic analyses provided some clues to the proteins' roles and predicted that the complex include cytoplasmic and membrane-associated proteins, ATPases, lipoproteins and substrates. These analyses also detected some similarity to bacteriophage proteins, but experimental confirmation, particularly of their biochemical function, was missing.
Leiman et al. 1 , part of PSI NYSGXRC, used crystallography to solve the structure of the amino-terminal fragment of the Escherichia coli CFT073 VgrG protein, which is encoded by open reading frame c3393. They found that despite having only 13% sequence identity to the T4 bacteriophage's cell-puncturing gp5–gp27 complex, VgrG is remarkably similar to it in structure: the VgrG structure corresponds roughly to a fusion of the two T4 proteins.
This group also reexamined the previously published crystal structure of the most abundant Type VI secretion-system protein, Hcp1. This protein forms donut-shaped hexamers that stack on top of each other to form a tube with an external diameter of 85 Å and an internal one of 40 Å. The structure of Hcp1 is very similar to gp27, which multimerizes to form the tandem tube domain that interacts with the T4 tail proteins themselves. It is also almost identical in diameter to the bacteriophage T4 tail-tube protein gp19.
Pell et al. 2 used NMR spectroscopy to uncover the structure of another protein of the Type VI secretion system, this time a gpV major tail protein from phage lambda. The gpV tail-tube protein of phage lambda is functionally analogous to T4 phage gp19, and Pell et al. found that the structure of gpV is similar to that of Hcp1.
Together, these papers provide good evidence that the proteins in the Type VI secretion-system apparatus assemble into a large multicomponent structure that is structurally and probably functionally similar to a bacteriophage tail. Putting all the pieces together, the Type VI secretion system can be thought of as an upside-down bacteriophage tail complex.
The similarity between the Type VI secretion system and bacteriophage tails raises the interesting question of which came first — the bacterial secretion system or the phage tails? Unfortunately we don't know... yet.
