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

<div class='caption-title'>Structure of P140.</div>
<div class='caption-title'>Closed conformation of the P140–P110 heterodimers by X-ray and cryo-EM.</div>
<div class='caption-title'>The structure of Nap by single-particle cryo-EM and in situ cryo-ET.</div>
Aparicio D, Scheffer MP, Marcos-Silva M, Vizarraga D, Sprankel L, Ratera M, Weber MS, Seybert A, Torres-Puig S, Gonzalez-Gonzalez L, Reitz J, Querol E, Piñol J, Pich OQ, Fita I, Frangakis AS
OpenAccess logo Nat Commun 11 2877 (2020)
Related entries: 6rut, 6s3u

Cited: 13 times
EuropePMC logo PMID: 32513917

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.

Reviews citing this publication (5)

  1. How bacteria utilize sialic acid during interactions with the host: snip, snatch, dispatch, match and attach. Jennings MP, Day CJ, Atack JM. Microbiology (Reading) 168 (2022)
  2. Maternal Infection and Preterm Birth: From Molecular Basis to Clinical Implications. Daskalakis G, Psarris A, Koutras A, Fasoulakis Z, Prokopakis I, Varthaliti A, Karasmani C, Ntounis T, Domali E, Theodora M, Antsaklis P, Pappa KI, Papapanagiotou A. Children (Basel) 10 907 (2023)
  3. Molecular Tools for Typing Mycoplasma pneumoniae and Mycoplasma genitalium. Dumke R. Front Microbiol 13 904494 (2022)
  4. Pathogenicity and virulence of Mycoplasma genitalium: Unraveling Ariadne's Thread. Yueyue W, Feichen X, Yixuan X, Lu L, Yiwen C, Xiaoxing Y. Virulence 13 1161-1183 (2022)
  5. Mycoplasma genitalium infection in the female reproductive system: Diseases and treatment. Yu J, Zhou Y, Luo H, Su X, Gan T, Wang J, Ye Z, Deng Z, He J. Front Microbiol 14 1098276 (2023)

Articles citing this publication (8)

  1. ArtiaX: An electron tomography toolbox for the interactive handling of sub-tomograms in UCSF ChimeraX. Ermel UH, Arghittu SM, Frangakis AS. Protein Sci 31 e4472 (2022)
  2. Immunodominant proteins P1 and P40/P90 from human pathogen Mycoplasma pneumoniae. Vizarraga D, Kawamoto A, Matsumoto U, Illanes R, Pérez-Luque R, Martín J, Mazzolini R, Bierge P, Pich OQ, Espasa M, Sanfeliu I, Esperalba J, Fernández-Huerta M, Scheffer MP, Pinyol J, Frangakis AS, Lluch-Senar M, Mori S, Shibayama K, Kenri T, Kato T, Namba K, Fita I, Miyata M, Aparicio D. Nat Commun 11 5188 (2020)
  3. Force and Stepwise Movements of Gliding Motility in Human Pathogenic Bacterium Mycoplasma pneumoniae. Mizutani M, Sasajima Y, Miyata M. Front Microbiol 12 747905 (2021)
  4. Molecular ruler of the attachment organelle in Mycoplasma pneumoniae. Nakane D, Murata K, Kenri T, Shibayama K, Nishizaka T. PLoS Pathog 17 e1009621 (2021)
  5. Mycoplasma genitalium Protein of Adhesion Promotes the Early Proliferation of Human Urothelial Cells by Interacting with RPL35. Dai P, Deng X, Liu P, Li L, Luo D, Liao Y, Zeng Y. Pathogens 10 1449 (2021)
  6. Alternative conformation of the C-domain of the P140 protein from Mycoplasma genitalium. Vizarraga D, Pérez-Luque R, Martín J, Fita I, Aparicio D. Acta Crystallogr F Struct Biol Commun 76 508-516 (2020)
  7. Cryo-electron tomography reveals the binding and release states of the major adhesion complex from Mycoplasma genitalium. Sprankel L, Scheffer MP, Manger S, Ermel UH, Frangakis AS. PLoS Pathog 19 e1011761 (2023)
  8. Genotyping of Mycoplasma pneumoniae strains isolated in Japan during 2019 and 2020: spread of p1 gene type 2c and 2j variant strains. Kenri T, Yamazaki T, Ohya H, Jinnai M, Oda Y, Asai S, Sato R, Ishiguro N, Oishi T, Horino A, Fujii H, Hashimoto T, Nakajima H, Shibayama K. Front Microbiol 14 1202357 (2023)


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