From self sufficiency to dependence: mechanisms and factors important for autotransporter biogenesis

Abstract

Autotransporters are a superfamily of proteins that use the type V secretion pathway for their delivery to the surface of Gram-negative bacteria. At first glance, autotransporters look to contain all the functional elements required to promote their own secretion: an amino-terminal signal peptide to mediate translocation across the inner membrane, a central passenger domain that is the secreted functional moiety, and a channel-forming carboxyl terminus that facilitates passenger domain translocation across the outer membrane. However, recent discoveries of common structural themes, translocation intermediates and accessory interactions have challenged the perceived simplicity of autotransporter secretion. Here, we discuss how these studies have led to an improved understanding of the mechanisms responsible for autotransporter biogenesis.

A mortise–tenon joint in the transmembrane domain modulates autotransporter assembly into bacterial outer membranes

“…Secretion of autotransporter passenger domains across the outer membrane requires that, ultimately, the polypeptide has extended through an aqueous channel that is formed by the barrel domain 5 . Thus, unlike other b-barrel proteins, the folding of an autotransporter barrel domain needs to proceed in a controlled fashion that also allows positioning of a segment of the passenger domain within the barrel domain lumen: in the correct structural context, and before the first and last b-strands anneal with each other to close the barrel domain.…”

“…Most autotransporters have large, b-helical passenger domains that are presented on the extracellular surface of bacterial cells; some of these passenger domains remain attached to the surface to function as adhesins, while others are proteolytically processed and released into the environment as effector proteins [1][2][3][4] . The folding of autotransporters is complex, requiring coordination of three reactions, namely (i) the completion of a 12-stranded carboxyterminal (C-terminal) b-sheet that will wrap to form a b-barrel, but ensuring that (ii) segments of the amino-terminal (Nterminal) domain are entrapped in the luminal cavity of the C-terminal barrel domain and (iii) the folding of the N-terminal passenger domain into its functional form 5 .…”

“…A range of methods have been used to address the folding state of autotransporters in their transit through the periplasm and initiation of assembly into the outer membrane [5][6][7][8] . Several lines of evidence indicate that a threading reaction enabling the passenger domain to emerge from the b-barrel can be completed after insertion into the outer membrane [8][9][10][11][12] .…”

Mechanistic link between β barrel assembly and the initiation of autotransporter secretion

“…Furthermore, our results provide evidence that the Bam complex catalyzes the membrane integration of β barrel proteins in a multistep process that can be perturbed by minor structural defects in client proteins. A utotransporters are a very large superfamily of virulence factors produced by Proteobacteria and Chlamydia that consist of an N-terminal extracellular domain (passenger domain) and a C-terminal β barrel domain (β domain) that anchors the protein to the outer membrane (OM) (1). Passenger domains range in size from ∼20 kDa to over 400 kDa and have been shown to mediate a variety of different virulence functions (2).…”

Adhesive Properties of YapV and Paralogous Autotransporter Proteins of Yersinia pestis

“…The "autotransporter" designation was given to specific outer membrane proteins based on the early assumption that they extrude their N-terminal end or passenger domain through a channel formed by their membrane-embedded C-terminal ␤-barrel domain (20). More recent work indicates that the Bam proteins and possibly TAM (translocation assembly module) proteins participate in this process (21)(22)(23).…”