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

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 angstrom, 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. The adhesion complex (Nap) in Mycoplasma genitalium is composed of the adhesin proteins P110 and P140 and essential for infectivity, motility and adhesion of this human pathogen. Here, the author present the structures of P140 alone and the P140/P110 complex in closed and open conformations and based on their structural data and further functional studies propose a mechanism for the attachment and release of M. genitalium to the host cell receptor.