Abstract
Autotransporters are secreted proteins that are assembled into the outer membrane of bacterial cells. The passenger domains of autotransporters are crucial for bacterial pathogenesis, with some remaining attached to the bacterial surface while others are released by proteolysis. An enigma remains as to whether autotransporters should be considered a class of secretion system, or simply a class of substrate with peculiar requirements for their secretion. We sought to establish a sensitive search protocol that could identify and characterize diverse autotransporters from bacterial genome sequence data. The new sequence analysis pipeline identified more than 1500 autotransporter sequences from diverse bacteria, including numerous species of Chlamydiales and Fusobacteria as well as all classes of Proteobacteria. Interrogation of the proteins revealed that there are numerous classes of passenger domains beyond the known proteases, adhesins and esterases. In addition the barrel-domain-a characteristic feature of autotransporters-was found to be composed from seven conserved sequence segments that can be arranged in multiple ways in the tertiary structure of the assembled autotransporter. One of these conserved motifs overlays the targeting information required for autotransporters to reach the outer membrane. Another conserved and diagnostic motif maps to the linker region between the passenger domain and barrel-domain, indicating it as an important feature in the assembly of autotransporters.
Highlights
Bacteria have an extraordinarily diverse array of protein secretion systems [1,2,3,4]
Hidden Markov Models Help Define the Distribution of Autotransporters in Bacteria We sought a new strategy based on hidden Markov models (HMMs) to identify autotransporters encoded within genome sequence data
This ‘‘AT47-HMM’’ was used to screen more than a thousand bacterial and archeal genomes from which 373 putative autotransporters were identified with high confidence, using an E-value of 1025 as a cut-off
Summary
Bacteria have an extraordinarily diverse array of protein secretion systems [1,2,3,4]. The necessity to rationalize the classification systems is exemplified even in the structurally-simplest system, the Type V secretion system, where new discoveries about structure, function and assembly mechanisms have expanded the classification such that it currently includes the Type Va ‘‘autotransporters’’, Type Vb ‘‘two-partner systems’’, Type Vc ‘‘trimeric autotransporters’’, Type Vd ‘‘Patatin-like proteins’’ [5] and Type Ve ‘‘intimins and invasins’’ (Buchanan S.K., personal communication). The Type Va group of proteins, the autotransporters, are defined by three domains: (i) a signal sequence at the N-terminus that enables targeting of the polypeptide to the inner membrane and through into the periplasm, (ii) the secreted passenger domain which encodes the effector function of each autotransporter, and (iii) the b-barrel ‘‘translocation domain’’, hereafter referred to as the barrel-domain, consisting of a short a-helical linker segment and 12 b-strands that are assembled into a b-barrel in the outer membrane [6,7,8,9,10]. The passenger domains secreted via the autotransporter mechanism mediate virulence through quite distinct biochemical activities: mediating physical adhesion via protein-protein interactions (‘‘adhesins’’), proteolytic degradation of select host proteins (‘‘proteases’’), lipolytic attack of host cell membranes (‘‘esterases’’) [10,11]-and perhaps other as yet uncharacterized activities as well
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