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 P...

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Detalhes bibliográficos
Autores: Aparicio Alarcón, David|||0000-0002-1971-5335, Scheffer, Margot P., Marcos Silva, Marina|||0000-0002-1816-3268, Vizarraga, David|||0000-0002-4478-0155, Sprankel, Lasse, Ratera, Mercè|||0000-0001-5224-9172, Weber, Miriam S.|||0000-0003-2125-8222, Seybert, Anja, Torres Puig, Sergi|||0000-0002-8976-6488, Gonzalez-Gonzalez, Luis|||0000-0002-5853-967X, Reitz, Julian, Querol Murillo, Enrique|||0000-0002-3658-3434, Piñol Ribas, Jaume|||0000-0002-9055-8934, Quijada Pich, Oscar|||0000-0003-3561-630X, Fita, Ignacio|||0000-0002-7521-2679, Frangakis, Achilleas S.|||0000-0002-8067-6611
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:252650
Acesso em linha:https://ddd.uab.cat/record/252650
https://dx.doi.org/urn:doi:10.1038/s41467-020-16511-2
Access Level:acceso abierto
Palavra-chave:Cryoelectron microscopy
Cryoelectron tomography
Microbiology
Pathogens
X-ray crystallography
Descrição
Resumo: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.