Coupling Factors in Macromolecular Type-IV Secretion Machineries

Abstract

Type IV secretion systems (T4SSs) are bacterial multiprotein organelles specialised in the transfer of (nucleo)protein complexes across cell membranes. They are essential for conjugation, bacterial-induced tumour formation in plant cells, as observed in Agrobacterium, toxin secretion, like in Bordetella and Helicobacter, cell-to-cell translocation of virulence factors, and intracellular activity of mammalian pathogens like Legionella. By enabling conjugative DNA delivery, these systems contribute to the spread of antibiotic resistance genes among bacteria. These translocons are made up by 10-15 proteins that are analogous to Vir proteins of Agrobacterium and traverse both membranes and the periplasmic space in between in Gram-negative bacteria. Their secretion substrates range from single-stranded DNA / protein complexes to multicomponent toxins and they are assisted by integral inner-membrane coupling factors, the multimeric type-IV coupling proteins (T4CPs), to connect the macromolecular complexes to be transferred with the secretory conduit. To do so, these T4CPs may be required to localise close to the secretion machinery within the donor cell. The T4CP structural prototype is the hexameric protein TrwB of Escherichia coli conjugative plasmid R388, closely related to Agrobacterium VirD4 protein. It is responsible for coupling the relaxosome with the DNA transport apparatus during cell mating. T4CP family members are related to SpoIIIE/FtsK proteins, essential for DNA pumping during sporulation and cell division. These features suggest possible mechanisms for conjugal T4CP function: as a simple coupler between two molecular machines, as a rotating device to pump DNA through the type-IV transport pore, or as a DNA injector, whereby its central channel would function as part of the transport pore.

Structure, function and latency regulation of a bacterial enterotoxin potentially derived from a mammalian adamalysin/ADAM xenolog

“…Such gene shuffling is common within and across bacteria and archaea and examples include the transfer of resistance plasmids (38). Contrary, documented transfer from bacteria to eukaryotic cells is restricted to few examples, among them the interaction between Agrobacterium tumefaciens and plant cells, which leads to Crown-Gall disease (39,40). Lastly, gene transfer from eukaryotes to bacteria is extremely uncommon and only detectable through phylogenetic and comparative genome analyses (41,42).…”

Biological Diversity of Prokaryotic Type IV Secretion Systems

“…1). The T4CP physically interacts with the translocation channel, which is comprised of the mating-pair formation (Mpf) proteins (62,114,169,237). Two types of Mpf proteins, an ATPase and a polytopic membrane subunit, are associated with all T4SS, whereas other Mpf proteins are less phylogenetically conserved.…”

“…T4CPs are also associated with most effector translocator systems, and a T4CP is required for DNA release by the N. gonorrhoeae GGI. T4CPs have been the subject of several excellent reviews (63,114,169,237); therefore, only a brief update on T4CP biochemistry and subunit interactions is warranted. We will, however, highlight results of our analyses of T4CPs from phylogenetically distant organisms indicating that these proteins display extensive sequence heterogeneity and distinct domain architectures.…”

Mobile genetic elements in the genus Bacteroides, and their mechanism(s) of dissemination

“…The best characterized CPs are TrwB of plasmid R388 (Inc.W group), TraD of F plasmids (Inc.F group), TraG of RP4 plasmids (Inc.P group), and VirD4 of A. tumefaciens Ti plasmids. 107 These proteins share the following characteristics: (1) they are composed of transmembrane a-helices in their N-terminal region that mediate anchoring to the inner membrane. Indeed, they are integral inner membrane proteins.…”