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

The iron-regulated protein FrpD from Neisseria meningitidis is an outer membrane lipoprotein that interacts with very high affinity (K ~ 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 Ca, FrpC undergoes Ca -dependent protein trans-splicing that includes an autocatalytic cleavage of the Asp-Pro peptide bond and formation of an Asp-Lys isopeptide bond. Here, we report the high-resolution structure of FrpD and describe the structure-function relationships underlying the interaction between FrpD and FrpC. We identified FrpD residues involved in FrpC binding, which enabled localization of FrpD within the low-resolution SAXS model of the FrpD-FrpC complex. Moreover, the trans-splicing activity of FrpC resulted in covalent linkage of the FrpC fragment to plasma membrane proteins of epithelial cells in vitro, suggesting that formation of the FrpD-FrpC complex may be involved in the interaction of meningococci with the host cell surface.