Publication Date:
2014-03-29
Description:
Bacterial type IV secretion systems translocate virulence factors into eukaryotic cells, distribute genetic material between bacteria and have shown potential as a tool for the genetic modification of human cells. Given the complex choreography of the substrate through the secretion apparatus, the molecular mechanism of the type IV secretion system has proved difficult to dissect in the absence of structural data for the entire machinery. Here we use electron microscopy to reconstruct the type IV secretion system encoded by the Escherichia coli R388 conjugative plasmid. We show that eight proteins assemble in an intricate stoichiometric relationship to form an approximately 3 megadalton nanomachine that spans the entire cell envelope. The structure comprises an outer membrane-associated core complex connected by a central stalk to a substantial inner membrane complex that is dominated by a battery of 12 VirB4 ATPase subunits organized as side-by-side hexameric barrels. Our results show a secretion system with markedly different architecture, and consequently mechanism, to other known bacterial secretion systems.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998870/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3998870/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Low, Harry H -- Gubellini, Francesca -- Rivera-Calzada, Angel -- Braun, Nathalie -- Connery, Sarah -- Dujeancourt, Annick -- Lu, Fang -- Redzej, Adam -- Fronzes, Remi -- Orlova, Elena V -- Waksman, Gabriel -- 079605/Wellcome Trust/United Kingdom -- 098302/Wellcome Trust/United Kingdom -- MR/K012401/1/Medical Research Council/United Kingdom -- England -- Nature. 2014 Apr 24;508(7497):550-3. doi: 10.1038/nature13081. Epub 2014 Mar 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Institute of Structural and Molecular Biology, University College London and Birkbeck College, Malet Street, London WC1E 7HX, UK [2] [3]. ; 1] Institut Pasteur, G5 Biologie structurale de la secretion bacterienne and UMR 3528-CNRS, 25 rue du Docteur Roux, 75015 Paris, France [2]. ; Institute of Structural and Molecular Biology, University College London and Birkbeck College, Malet Street, London WC1E 7HX, UK. ; Institut Pasteur, G5 Biologie structurale de la secretion bacterienne and UMR 3528-CNRS, 25 rue du Docteur Roux, 75015 Paris, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24670658" target="_blank"〉PubMed〈/a〉
Keywords:
Adenosine Triphosphatases/chemistry/genetics/metabolism/ultrastructure
;
*Bacterial Secretion Systems/genetics
;
Cell Membrane/metabolism
;
Escherichia coli/*chemistry/cytology/genetics/*ultrastructure
;
Escherichia coli Proteins/chemistry/isolation &
;
purification/metabolism/ultrastructure
;
Microscopy, Electron
;
Models, Molecular
;
Multiprotein Complexes/chemistry/genetics/metabolism/ultrastructure
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
