The gp27-like Hub of VgrG Serves as Adaptor to Promote Hcp Tube Assembly

J Mol Biol. 2018 Sep 14;430(18 Pt B):3143-3156. doi: 10.1016/j.jmb.2018.07.018. Epub 2018 Jul 19.


Contractile injection systems are multiprotein complexes that use a spring-like mechanism to deliver effectors into target cells. In addition to using a conserved mechanism, these complexes share a common core known as the tail. The tail comprises an inner tube tipped by a spike, wrapped by a contractile sheath, and assembled onto a baseplate. Here, using the type VI secretion system (T6SS) as a model of contractile injection systems, we provide molecular details on the interaction between the inner tube and the spike. Reconstitution into the Escherichia coli heterologous host in the absence of other T6SS components and in vitro experiments demonstrated that the Hcp tube component and the VgrG spike interact directly. VgrG deletion studies coupled to functional assays showed that the N-terminal domain of VgrG is sufficient to interact with Hcp, to initiate proper Hcp tube polymerization, and to promote sheath dynamics and Hcp release. The interaction interface between Hcp and VgrG was then mapped using docking simulations, mutagenesis, and cysteine-mediated cross-links. Based on these results, we propose a model in which the VgrG base serves as adaptor to recruit the first Hcp hexamer and initiates inner tube polymerization.

Keywords: contractile mechanism; protein transport; spike; tail tube; type VI secretion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Disulfides
  • Hemolysin Proteins / chemistry*
  • Hemolysin Proteins / metabolism
  • Models, Molecular
  • Multiprotein Complexes / chemistry*
  • Multiprotein Complexes / metabolism
  • Protein Binding
  • Protein Conformation
  • Protein Interaction Domains and Motifs
  • Protein Multimerization
  • Structure-Activity Relationship
  • Type VI Secretion Systems


  • Bacterial Proteins
  • Disulfides
  • Hemolysin Proteins
  • Multiprotein Complexes
  • Type VI Secretion Systems