Structure of the calcium-dependent type 2 secretion pseudopilus

Nat Microbiol. 2017 Dec;2(12):1686-1695. doi: 10.1038/s41564-017-0041-2. Epub 2017 Oct 9.

Abstract

Many Gram-negative bacteria use type 2 secretion systems (T2SSs) to secrete proteins involved in virulence and adaptation. Transport of folded proteins via T2SS nanomachines requires the assembly of inner membrane-anchored fibres called pseudopili. Although efficient pseudopilus assembly is essential for protein secretion, structure-based functional analyses are required to unravel the mechanistic link between these processes. Here, we report an atomic model for a T2SS pseudopilus from Klebsiella oxytoca, obtained by fitting the NMR structure of its calcium-bound subunit PulG into the ~5-Å-resolution cryo-electron microscopy reconstruction of assembled fibres. This structure reveals the comprehensive network of inter-subunit contacts and unexpected features, including a disordered central region of the PulG helical stem, and highly flexible C-terminal residues on the fibre surface. NMR, mutagenesis and functional analyses highlight the key role of calcium in PulG folding and stability. Fibre disassembly in the absence of calcium provides a basis for pseudopilus length control, essential for protein secretion, and supports the Archimedes screw model for the type 2 secretion mechanism.

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Calcium / physiology*
  • Circular Dichroism
  • Cryoelectron Microscopy
  • Escherichia coli / genetics
  • Fimbriae, Bacterial / chemistry
  • Fimbriae, Bacterial / ultrastructure
  • Gram-Negative Bacteria / metabolism*
  • Isotope Labeling
  • Klebsiella oxytoca / metabolism*
  • Klebsiella oxytoca / ultrastructure
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Protein Conformation
  • Protein Folding
  • Protein Stability
  • Protein Transport
  • Type II Secretion Systems / chemistry
  • Type II Secretion Systems / metabolism*

Substances

  • Bacterial Proteins
  • Type II Secretion Systems
  • Calcium