2ypw Citations

Structure of a bacterial type IV secretion core complex at subnanometre resolution.


Type IV secretion (T4S) systems are able to transport DNAs and/or proteins through the membranes of bacteria. They form large multiprotein complexes consisting of 12 proteins termed VirB1-11 and VirD4. VirB7, 9 and 10 assemble into a 1.07 MegaDalton membrane-spanning core complex (CC), around which all other components assemble. This complex is made of two parts, the O-layer inserted in the outer membrane and the I-layer inserted in the inner membrane. While the structure of the O-layer has been solved by X-ray crystallography, there is no detailed structural information on the I-layer. Using high-resolution cryo-electron microscopy and molecular modelling combined with biochemical approaches, we determined the I-layer structure and located its various components in the electron density. Our results provide new structural insights on the CC, from which the essential features of T4S system mechanisms can be derived.

Reviews citing this publication (11)

  1. Mechanism and Function of Type IV Secretion During Infection of the Human Host. Gonzalez-Rivera C, Bhatty M, Christie PJ. Microbiol Spectr 4 (2016)
  2. Secretome of obligate intracellular Rickettsia. Gillespie JJ, Kaur SJ, Rahman MS, Rennoll-Bankert K, Sears KT, Beier-Sexton M, Azad AF. FEMS Microbiol. Rev. 39 47-80 (2015)
  3. Structural Biology of Bacterial Type IV Secretion Systems. Chandran Darbari V, Waksman G. Annu. Rev. Biochem. 84 603-629 (2015)
  4. Secretion systems in Gram-negative bacteria: structural and mechanistic insights. Costa TR, Felisberto-Rodrigues C, Meir A, Prevost MS, Redzej A, Trokter M, Waksman G. Nat. Rev. Microbiol. 13 343-359 (2015)
  5. Structural biology of the Gram-negative bacterial conjugation systems. Ilangovan A, Connery S, Waksman G. Trends Microbiol. 23 301-310 (2015)
  6. Type IV secretion systems and genomic islands-mediated horizontal gene transfer in Pseudomonas and Haemophilus. Juhas M. Microbiol. Res. 170 10-17 (2015)
  7. Mechanism and structure of the bacterial type IV secretion systems. Christie PJ, Whitaker N, González-Rivera C. Biochim. Biophys. Acta 1843 1578-1591 (2014)
  8. Social behavior and decision making in bacterial conjugation. Koraimann G, Wagner MA. Front Cell Infect Microbiol 4 54 (2014)
  9. Recent advances in the structural and molecular biology of type IV secretion systems. Trokter M, Felisberto-Rodrigues C, Christie PJ, Waksman G. Curr. Opin. Struct. Biol. 27 16-23 (2014)
  10. Structural organisation of the type IV secretion systems. Waksman G, Orlova EV. Curr. Opin. Microbiol. 17 24-31 (2014)
  11. Echoes of a distant past: The cag pathogenicity island of Helicobacter pylori. Pacchiani N, Censini S, Buti L, Covacci A. Cold Spring Harb Perspect Med 3 (2013)

Articles citing this publication (17)

  1. A general protocol for the generation of Nanobodies for structural biology. Pardon E, Laeremans T, Triest S, Rasmussen SG, Wohlkönig A, Ruf A, Muyldermans S, Hol WG, Kobilka BK, Steyaert J. Nat Protoc 9 674-693 (2014)
  2. Structure of a type IV secretion system. Low HH, Gubellini F, Rivera-Calzada A, Braun N, Connery S, Dujeancourt A, Lu F, Redzej A, Fronzes R, Orlova EV, Waksman G. Nature 508 550-553 (2014)
  3. Key components of the eight classes of type IV secretion systems involved in bacterial conjugation or protein secretion. Guglielmini J, Néron B, Abby SS, Garcillán-Barcia MP, de la Cruz F, Rocha EP. Nucleic Acids Res. 42 5715-5727 (2014)
  4. Probing a cell-embedded megadalton protein complex by DNP-supported solid-state NMR. Kaplan M, Cukkemane A, van Zundert GC, Narasimhan S, Daniëls M, Mance D, Waksman G, Bonvin AM, Fronzes R, Folkers GE, Baldus M. Nat. Methods 12 649-652 (2015)
  5. Native structure of a type IV secretion system core complex essential for Legionella pathogenesis. Kubori T, Koike M, Bui XT, Higaki S, Aizawa S, Nagai H. Proc. Natl. Acad. Sci. U.S.A. 111 11804-11809 (2014)
  6. Molecular and structural analysis of Legionella DotI gives insights into an inner membrane complex essential for type IV secretion. Kuroda T, Kubori T, Thanh Bui X, Hyakutake A, Uchida Y, Imada K, Nagai H. Sci Rep 5 10912 (2015)
  7. Two novel membrane proteins, TcpD and TcpE, are essential for conjugative transfer of pCW3 in Clostridium perfringens. Wisniewski JA, Teng WL, Bannam TL, Rood JI. J. Bacteriol. 197 774-781 (2015)
  8. Nanobodies to Study G Protein-Coupled Receptor Structure and Function. Manglik A, Kobilka BK, Steyaert J. Annu. Rev. Pharmacol. Toxicol. 57 19-37 (2017)
  9. Structural Insight into How Bacteria Prevent Interference between Multiple Divergent Type IV Secretion Systems. Gillespie JJ, Phan IQ, Scheib H, Subramanian S, Edwards TE, Lehman SS, Piitulainen H, Rahman MS, Rennoll-Bankert KE, Staker BL, Taira S, Stacy R, Myler PJ, Azad AF, Pulliainen AT. MBio 6 e01867-15 (2015)
  10. The type IV secretion protein TraK from the Enterococcus conjugative plasmid pIP501 exhibits a novel fold. Goessweiner-Mohr N, Fercher C, Arends K, Birner-Gruenberger R, Laverde-Gomez D, Huebner J, Grohmann E, Keller W. Acta Crystallogr. D Biol. Crystallogr. 70 1124-1135 (2014)
  11. Structure of the Bacterial Sex F Pilus Reveals an Assembly of a Stoichiometric Protein-Phospholipid Complex. Costa TRD, Ilangovan A, Ukleja M, Redzej A, Santini JM, Smith TK, Egelman EH, Waksman G. Cell 166 1436-1444.e10 (2016)
  12. TraK and TraB are conserved outer membrane proteins of the Neisseria gonorrhoeae Type IV secretion system and are expressed at low levels in wild-type cells. Ramsey ME, Hackett KT, Bender T, Kotha C, van der Does C, Dillard JP. J. Bacteriol. 196 2954-2968 (2014)
  13. Structure of the double-stranded DNA-binding type IV secretion protein TraN from Enterococcus. Goessweiner-Mohr N, Eder M, Hofer G, Fercher C, Arends K, Birner-Gruenberger R, Grohmann E, Keller W. Acta Crystallogr. D Biol. Crystallogr. 70 2376-2389 (2014)
  14. The Rickettsia type IV secretion system: unrealized complexity mired by gene family expansion. Gillespie JJ, Phan IQ, Driscoll TP, Guillotte ML, Lehman SS, Rennoll-Bankert KE, Subramanian S, Beier-Sexton M, Myler PJ, Rahman MS, Azad AF. Pathog Dis 74 (2016)
  15. The Brucella suis IbpA heat-shock chaperone is not required for virulence or for expression of the VirB type IV secretion system VirB8 protein. Berta P, Bourg G, Hanna N, Saadeh B, Armengaud J, Patey G, O'Callaghan D. Lett. Appl. Microbiol. 58 564-568 (2014)
  16. HDX-MS and deletion analysis of the type 4 secretion system protein TraF from the Escherichia coli F plasmid. Lento C, Ferraro M, Wilson D, Audette GF. FEBS Lett. 590 376-386 (2016)
  17. Peptidomimetic Small Molecules Disrupt Type IV Secretion System Activity in Diverse Bacterial Pathogens. Shaffer CL, Good JA, Kumar S, Krishnan KS, Gaddy JA, Loh JT, Chappell J, Almqvist F, Cover TL, Hadjifrangiskou M. MBio 7 e00221-16 (2016)

Related citations provided by authors (1)

  1. Structure of a type IV secretion system core complex.. Fronzes R, Schäfer E, Wang L, Saibil HR, Orlova EV, Waksman G Science 323 266-8 (2009)