Research

Type 4 Secretion Systems (T4SS)

These systems are present in both Gram-negative and Gram- positive bacteria. They form multi-megaDalton machines embedded in membranes and are responsible for the secretion of both proteins and nucleic acid substrates. They play major roles in pathogenicity of, for example, Helicobacter pylori, the causative agent of ulcers. They also mediate transfer of plasmid DNAs during conjugation, a process that leads to the spread of antibiotics resistance genes. T4S systems are composed of 12 proteins named VirB1-11 and VirD4 that assemble into a formidable nanomachine of more than 3 megaDalton in size and spanning the two membranes of Gram-negative bacteria.

References

Download a recent review and our landmark papers in Nature, Science and Cell. Mace   K,   Vaddakepat   A,   Redzej   A,   Lukoyanova   N,   Oomen   C,   Braun   N,   Ukeja   M,   Lu   F,   Costa   T,   Orlova   E,   Baker   D,   Cong   Q,   Waksman   G   (2022). Cryo-EM structure of a type IV secretion system . Nature . 607:191-196. Ilangovan A,   Kay,   C,   Roier   S,   Mkami   H,   Salvadori   E,   Zechner   E,   Zanetti   G,   Waksman   G    (2017).   Cryo-EM   structure   of   a   relaxase   reveals   the molecular basis of DNA unwinding during bacterial conjugation . Cell . 169:708-721. Costa   TR,   Ilangovan A,   Ukleja   M,   Redzej A,   Santini   JM,   Smith   TK,   Egelman   EH,   Waksman   G    (2016).   Structure   of   the   Bacterial   Sex   F   Pilus Reveals an Assembly of a Stoichiometric Protein-Phospholipid Complex . Cell. 166:1436-1444.e10 Trokter   M,   Felisberto-Rodrigues   C,   Christie   PJ   and   Waksman   G    (2014) .   Recent   advances   in   the   structural   and   molecular   biology   of   type   IV secretion systems . Curr Opin Struct Biol . 2014 Aug;27:16-23. doi: 10.1016/j.sbi.2014.02.006. Epub 2014 Apr 5.  Low   HH,   Gubellini   F,   Rivera-Calzada   A,   Braun   N,   Connery   S,   Dujeancourt   A,   Lu   F,   Redzej   A,   Fronzes   R,   Orlova   EV,   Waksman   G    (2014). Structure of a type IV secretion system . Nature . 2014 Apr 24;508(7497):550-3. doi: 10.1038/nature13081. Epub 2014 Mar 9 Chandran,   R.   Fronzes,   S.   Duquerroy,   N.   Cronin,   J.   Navaza,   and   G.   Waksman    (2009).   Crystal   structure   of   the   outer   membrane   complex   of a type IV secretion system . Nature . 462:1011-1015 R. Fronzes, E. Schaefer, H. Saibil, E. Orlova and G. Waksman  (2009). Structure of type IV secretion core complex.   Science . 323:266-268.