Structure and mechanism of the Nap adhesion complex from the human pathogen Mycoplasma genitalium

Nat Commun. 2020 Jun 8;11(1):2877. doi: 10.1038/s41467-020-16511-2.

Abstract

Mycoplasma genitalium is a human pathogen adhering to host target epithelial cells and causing urethritis, cervicitis and pelvic inflammatory disease. Essential for infectivity is a transmembrane adhesion complex called Nap comprising proteins P110 and P140. Here we report the crystal structure of P140 both alone and in complex with the N-terminal domain of P110. By cryo-electron microscopy (cryo-EM) and tomography (cryo-ET) we find closed and open Nap conformations, determined at 9.8 and 15 Å, respectively. Both crystal structures and the cryo-EM structure are found in a closed conformation, where the sialic acid binding site in P110 is occluded. By contrast, the cryo-ET structure shows an open conformation, where the binding site is accessible. Structural information, in combination with functional studies, suggests a mechanism for attachment and release of M. genitalium to and from the host cell receptor, in which Nap conformations alternate to sustain motility and guarantee infectivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Adhesion*
  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism*
  • Bacterial Proteins / ultrastructure
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Mutation / genetics
  • Mycoplasma genitalium / metabolism*
  • Protein Domains
  • Protein Multimerization
  • Protein Structure, Secondary
  • Structure-Activity Relationship

Substances

  • Bacterial Proteins