Trends in Microbiology
Volume 6, Issue 9, 1 September 1998, Pages 370-378
Journal home page for Trends in Microbiology

The great escape: structure and function of the autotransporter proteins

https://doi.org/10.1016/S0966-842X(98)01318-3Get rights and content

Abstract

The autotransporters, a family of secreted proteins from Gram-negative bacteria, possess an overall unifying structure comprising three functional domains: the amino-terminal leader sequence, the secreted mature protein (passenger domain) and a carboxy-terminal (β-) domain that forms a β-barrel pore to allow secretion of the passenger protein. Members of this family have been implicated as important or putative virulence factors in many Gram-negative pathogens.

Section snippets

Mechanisms of secretion in gram-negative bacteria

Several secretion systems in Gram-negative bacteria have been studied extensively. The so-called type I secretion systems are exemplified by the HlyA hemolysin of Escherichia coli. HlyA is secreted through the inner and outer membrane via an oligomeric complex composed of a large ATP-binding cassette (ABC) transporter (HlyB), an accessory factor (HlyD) and an additional outer membrane factor (TolC)[2].

The type II secretion system is a two-step process and has been best studied for the

The autotransporter secretion mechanism

The autotransporter secretion system, as distinct from the mechanisms detailed above, was first described for the IgA1 proteases of Neisseria gonorrhoeae by Pohlner et al.1, 6, who elegantly elucidated the fundamental mechanism. (The term `type IV secretion' has been proposed for the autotransporter proteins[4]. We favor the use of this term; however, autotransporter is a more descriptive designation and will be used throughout this review.) During secretion, the Iga polyprotein precursor is

Function and phylogeny of the autotransporters

The passenger domains of autotransporters are widely divergent, yet phylogenic relationships can be inferred. Conservation of the serine protease motif (consensus GDSGSP) at similar positions in the E. coli proteins Pet (Ref. [32]), Tsh (Ref. [30]), EspP (Ref. [8]) and EspC (Ref. [33]) and the Shigella proteins ShMu (Ref. [34]) and SepA (Ref. [29]) strongly suggests that these proteins are related serine proteases. In fact, these proteins comprise a subfamily of the autotransporters, for which

Potential biotechnological applications

One compelling feature of autotransporter proteins is their promise as tools for the analysis of macromolecular interactions. Possible applications include the expression of (1) antigenic determinants for vaccine development, (2) peptide libraries for epitope mapping or antibody specificity tests and (3) receptors or ligands for binding assays or simple protein purification.

Autotransporter molecules would theoretically allow nearly any protein antigen to be expressed from a Gram-negative

Conclusions

Notwithstanding the controversies regarding the specifics of structure and function, there is an overall unifying structure for the autotransporter molecules, which is intrinsically associated with their mode of biogenesis. The defining but still hypothetical characteristics are that the β-domain forms a β-barrel structure within the outer membrane and that the passenger protein is translocated to the cell surface via the autogenous pore. Further experimental analyses are required to clarify

Acknowledgements

Work in the laboratory of J.P.N. is supported by Public Health Service grant AI-33096. We thank James B. Kaper and Harry L.T. Mobley for helpful review of the manuscript.

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