Structural insights into the secretin translocation channel in the type II secretion system

Nat Struct Mol Biol. 2017 Feb;24(2):177-183. doi: 10.1038/nsmb.3350. Epub 2017 Jan 9.

Abstract

The secretin GspD of the type II secretion system (T2SS) forms a channel across the outer membrane in Gram-negative bacteria to transport substrates from the periplasm to the extracellular milieu. The lack of an atomic-resolution structure of the GspD channel hinders the investigation of substrate translocation mechanism of T2SS. Here we report cryo-EM structures of two GspD channels (∼1 MDa), from Escherichia coli K12 and Vibrio cholerae, at ∼3 Å resolution. The structures reveal a pentadecameric channel architecture, wherein three rings of GspD N domains form the periplasmic channel. The secretin domain constitutes a novel double β-barrel channel, with at least 60 β-strands in each barrel, and is stabilized by S domains. The outer membrane channel is sealed by β-strand-enriched gates. On the basis of the partially open state captured, we proposed a detailed gate-opening mechanism. Our structures provide a structural basis for understanding the secretin superfamily and the mechanism of substrate translocation in T2SS.

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence
  • Cryoelectron Microscopy
  • Escherichia coli / ultrastructure
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / ultrastructure*
  • Ion Channel Gating
  • Models, Molecular
  • Porins / ultrastructure*
  • Protein Conformation, beta-Strand
  • Protein Interaction Domains and Motifs
  • Protein Structure, Quaternary
  • Secretin / chemistry
  • Type II Secretion Systems / chemistry
  • Type II Secretion Systems / ultrastructure*

Substances

  • Escherichia coli Proteins
  • GspD protein, E coli
  • Porins
  • Type II Secretion Systems
  • Secretin