Remodelling of VipA/VipB tubules by ClpV-mediated threading is crucial for type VI protein secretion.
The recently identified type VI secretion systems (T6SS) have a crucial function in the virulence of various proteobacteria, including the human pathogen Vibrio cholerae. T6SS are encoded by a conserved gene cluster comprising approximately 15 open reading frames, mediating the appearance of Hcp and VgrG proteins in cell culture supernatants. Here, we analysed the function of the V. cholerae T6SS member ClpV, a specialized AAA+ protein. ClpV is crucial for a functional T6SS and interacts through its N-terminal domain with the VipA/VipB complex that is composed of two conserved and essential members of T6SS. Transferring ClpV substrate specificity to a distinct AAA+ protein involved in proteolysis caused degradation of VipA but not Hcp or VgrG2, suggesting that VipA rather than Hcp/VgrG2 functions as a primary ClpV substrate. Strikingly, VipA/VipB form tubular, cogwheel-like structures that are converted by a threading activity of ClpV into small complexes. ClpV-mediated remodelling of VipA/VipB tubules represents a crucial step in T6S, illuminating an unexpected role of an ATPase component in protein secretion.
Bönemann
Gabriele
G
Zentrum für Molekulare Biologie Heidelberg, DKFZ-ZMBH Alliance, Universität Heidelberg, Heidelberg, Germany.
Pietrosiuk
Aleksandra
A
Diemand
Alexander
A
Zentgraf
Hanswalter
H
Mogk
Axel
A
D000251:Adenosine Triphosphatases / Q000502:physiology*; D001426:Bacterial Proteins / Q000378:metabolism; D001692:Biological Transport; D002352:Carrier Proteins / Q000502:physiology*; D015964:Gene Expression Regulation, Bacterial; D008854:Microscopy, Electron; D018832:Molecular Chaperones / Q000378:metabolism; D005810:Multigene Family; D016366:Open Reading Frames; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014734:Vibrio cholerae / Q000378:metabolism*; D014774:Virulence; D037521:Virulence Factors / Q000378:metabolism
D001426:Bacterial Proteins; D002352:Carrier Proteins; D018832:Molecular Chaperones; D037521:Virulence Factors; D000251:Adenosine Triphosphatases