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

Nature Communications
David AparicioAchilleas S Frangakis

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.

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Citations

Oct 16, 2020·Nature Communications·David VizarragaDavid Aparicio
Nov 3, 2020·Acta Crystallographica. Section F, Structural Biology Communications·David VizarragaDavid Aparicio
Feb 18, 2021·Trends in Microbiology·David VizarragaOscar Q Pich
Jun 11, 2021·PLoS Pathogens·Daisuke NakaneTakayuki Nishizaka
Oct 12, 2021·Frontiers in Microbiology·Masaki MizutaniMakoto Miyata

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Methods Mentioned

BETA
X-ray
fluorescence-activated cell sorting
surface plasmon resonance
PCR
light scattering
transmission electron microscopy
chip
Protein Assay
flow cytometry

Software Mentioned

CCP4i
Refmac5
ImageJ
FACSDiva
PISA
MTrack2
Phaser
CellQuest
Aimless
- Pro

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