Biogenesis and structure of a type VI secretion membrane core complex

Nature. 2015 Jul 30;523(7562):555-60. doi: 10.1038/nature14667. Epub 2015 Jul 22.


Bacteria share their ecological niches with other microbes. The bacterial type VI secretion system is one of the key players in microbial competition, as well as being an important virulence determinant during bacterial infections. It assembles a nano-crossbow-like structure in the cytoplasm of the attacker cell that propels an arrow made of a haemolysin co-regulated protein (Hcp) tube and a valine-glycine repeat protein G (VgrG) spike and punctures the prey's cell wall. The nano-crossbow is stably anchored to the cell envelope of the attacker by a membrane core complex. Here we show that this complex is assembled by the sequential addition of three type VI subunits (Tss)-TssJ, TssM and TssL-and present a structure of the fully assembled complex at 11.6 Å resolution, determined by negative-stain electron microscopy. With overall C5 symmetry, this 1.7-megadalton complex comprises a large base in the cytoplasm. It extends in the periplasm via ten arches to form a double-ring structure containing the carboxy-terminal domain of TssM (TssMct) and TssJ that is anchored in the outer membrane. The crystal structure of the TssMct-TssJ complex coupled to whole-cell accessibility studies suggest that large conformational changes induce transient pore formation in the outer membrane, allowing passage of the attacking Hcp tube/VgrG spike.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Secretion Systems*
  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Crystallography, X-Ray
  • Cytoplasm / chemistry
  • Cytoplasm / metabolism
  • Escherichia coli / chemistry*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / biosynthesis
  • Escherichia coli Proteins / chemistry*
  • Lipopeptides / biosynthesis
  • Lipopeptides / chemistry*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / chemistry*
  • Microscopy, Electron
  • Models, Molecular
  • Multiprotein Complexes / biosynthesis*
  • Multiprotein Complexes / chemistry*
  • Periplasm / chemistry
  • Periplasm / metabolism
  • Porosity
  • Protein Structure, Tertiary
  • Protein Subunits / biosynthesis
  • Protein Subunits / chemistry


  • Bacterial Secretion Systems
  • Escherichia coli Proteins
  • Lipopeptides
  • Membrane Proteins
  • Multiprotein Complexes
  • Protein Subunits
  • TssJ protein, E coli
  • TssL protein, E coli
  • TssM protein, E coli

Associated data

  • PDB/4Y7L
  • PDB/4Y7M
  • PDB/4Y7O