title: 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.
authors.affiliation: Institut de Biologia Molecular de Barcelona, C.S.I.C., c/ Jordi Girona, 18-26, E-08034 Barcelona, Spain. xgrcri@ibmb.csic.es
authors.forename: F X
authors.initials: FX
authors.lastname: Gomis-Rüth
authors.forename: M
authors.initials: M
authors.lastname: Solà
authors.forename: F
authors.initials: F
authors.lastname: de la Cruz
authors.forename: M
authors.initials: M
authors.lastname: Coll
mesh_terms: D000818:Animals; D025243:Bacterial Proton-Translocating ATPases / Q000737:chemistry* / Q000145:classification* / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D003227:Conjugation, Genetic; D006801:Humans; D046911:Macromolecular Substances
chemical_list: D046911:Macromolecular Substances; D025243:Bacterial Proton-Translocating ATPases