Folding Control in the Path of Type 5 Secretion

Abstract

The type 5 secretion system (T5SS) is one of the more widespread secretion systems in Gram-negative bacteria. Proteins secreted by the T5SS are functionally diverse (toxins, adhesins, enzymes) and include numerous virulence factors. Mechanistically, the T5SS has long been considered the simplest of secretion systems, due to the paucity of proteins required for its functioning. Still, despite more than two decades of study, the exact process by which T5SS substrates attain their final destination and correct conformation is not totally deciphered. Moreover, the recent addition of new sub-families to the T5SS raises additional questions about this secretion mechanism. Central to the understanding of type 5 secretion is the question of protein folding, which needs to be carefully controlled in each of the bacterial cell compartments these proteins cross. Here, the biogenesis of proteins secreted by the Type 5 secretion system is discussed, with a focus on the various factors preventing or promoting protein folding during biogenesis.

The patatin-like protein PlpD forms novel structurally dynamic homodimers in thePseudomonas aeruginosaouter membrane

“…In this regard it is notable that the b-barrels of "autotransporters" (type Va and Vc pathways) play a role in the secretion of a covalently linked extracellular passenger domain at a relatively early stage of assembly when they form an open hybrid barrel with BamA [50,51], but have never been observed to promote passenger domain secretion once they are fully folded. Single passenger domains are secreted as a largely unfolded polypeptide that folds slowly in the extracellular space due to its unusual b-helical structure, whereas the three passenger domains of "trimeric" autotransporters fold coordinately into a coiled-coil structure [52]. The so-called exoproteins of two partner secretion (type Vb) pathways are secreted through a fully folded b-barrel protein that is a member of the Omp85 superfamily, but like the passenger domains of classical autotransporters are secreted by undergoing a transition from an unfolded state to a b-helix in the extracellular milieu [39].…”

A Review on Various Secretion Systems: A Versatile Molecular Weapon for Bacterial Pathogenesis, Special Reference to Type 7 Secretion System (T7SS) in Multi Drug Resistance Staphylococcus aureus.

“…Remnants of the autotransporters are trusted to be porins which form similar beta barrel structures. T5SS systems come in two types autotransporters proteins involve a single two domain polypeptide one of these domains is an outer membrane barrel protein and other is a passenger protein a well-studied example of this is Ag43 protein in E.coli [57,58]. The process begins with Sec secretion to periplasm as an unfolded protein it then spontaneously inserts itself into outer membrane pulls passenger domain through to cell surface, some auto transporter proteins remain this way while others undergo cleavage of passenger to secreted state both proteases and spontaneous processes can cause cleavage of extracellular domains from membrane bound barrel [59].…”

There Are No Insurmountable Barriers: Passage of the Helicobacter pylori VacA Toxin from Bacterial Cytoplasm to Eukaryotic Cell Organelle

“…The T5SS is regarded as the simplest and one of the most common secretion systems in Gram-negative bacteria. Based on gene organization and protein structure, six sub-classes of the T5SS are distinguished (Va-f) [ 54 ]. The VacA protein is classified as Va type, i.e., classical AT [ 3 ].…”