Structural basis of the interaction between the putative adhesion-involved and iron-regulated FrpD and FrpC proteins of Neisseria meningitidis

Sci Rep. 2017 Jan 13;7:40408. doi: 10.1038/srep40408.

Abstract

The iron-regulated protein FrpD from Neisseria meningitidis is an outer membrane lipoprotein that interacts with very high affinity (Kd ~ 0.2 nM) with the N-terminal domain of FrpC, a Type I-secreted protein from the Repeat in ToXin (RTX) protein family. In the presence of Ca2+, FrpC undergoes Ca2+ -dependent protein trans-splicing that includes an autocatalytic cleavage of the Asp414-Pro415 peptide bond and formation of an Asp414-Lys isopeptide bond. Here, we report the high-resolution structure of FrpD and describe the structure-function relationships underlying the interaction between FrpD and FrpC1-414. We identified FrpD residues involved in FrpC1-414 binding, which enabled localization of FrpD within the low-resolution SAXS model of the FrpD-FrpC1-414 complex. Moreover, the trans-splicing activity of FrpC resulted in covalent linkage of the FrpC1-414 fragment to plasma membrane proteins of epithelial cells in vitro, suggesting that formation of the FrpD-FrpC1-414 complex may be involved in the interaction of meningococci with the host cell surface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Bacterial Outer Membrane Proteins / metabolism
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / genetics
  • Cell Adhesion / genetics
  • Humans
  • Iron / chemistry
  • Iron / metabolism
  • Iron-Binding Proteins / chemistry*
  • Iron-Binding Proteins / metabolism
  • Lipoproteins / chemistry
  • Lipoproteins / metabolism
  • Membrane Proteins / chemistry*
  • Membrane Proteins / genetics
  • Neisseria meningitidis / chemistry*
  • Neisseria meningitidis / genetics
  • Periplasmic Binding Proteins / chemistry
  • Periplasmic Binding Proteins / metabolism
  • X-Ray Diffraction

Substances

  • Bacterial Outer Membrane Proteins
  • Bacterial Proteins
  • Iron-Binding Proteins
  • Lipoproteins
  • Membrane Proteins
  • Periplasmic Binding Proteins
  • frpC protein, Neisseria meningitidis
  • Iron