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Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila

Author

Listed:
  • Beatriz Trastoy

    (Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park)

  • Andreas Naegeli

    (Genovis AB)

  • Itxaso Anso

    (Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park)

  • Jonathan Sjögren

    (Genovis AB)

  • Marcelo E. Guerin

    (Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park
    IKERBASQUE, Basque Foundation for Science)

Abstract

Akkermansia muciniphila is a mucin-degrading bacterium commonly found in the human gut that promotes a beneficial effect on health, likely based on the regulation of mucus thickness and gut barrier integrity, but also on the modulation of the immune system. In this work, we focus in OgpA from A. muciniphila, an O-glycopeptidase that exclusively hydrolyzes the peptide bond N-terminal to serine or threonine residues substituted with an O-glycan. We determine the high-resolution X-ray crystal structures of the unliganded form of OgpA, the complex with the glycodrosocin O-glycopeptide substrate and its product, providing a comprehensive set of snapshots of the enzyme along the catalytic cycle. In combination with O-glycopeptide chemistry, enzyme kinetics, and computational methods we unveil the molecular mechanism of O-glycan recognition and specificity for OgpA. The data also contribute to understanding how A. muciniphila processes mucins in the gut, as well as analysis of post-translational O-glycosylation events in proteins.

Suggested Citation

  • Beatriz Trastoy & Andreas Naegeli & Itxaso Anso & Jonathan Sjögren & Marcelo E. Guerin, 2020. "Structural basis of mammalian mucin processing by the human gut O-glycopeptidase OgpA from Akkermansia muciniphila," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18696-y
    DOI: 10.1038/s41467-020-18696-y
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    Cited by:

    1. Joann Chongsaritsinsuk & Alexandra D. Steigmeyer & Keira E. Mahoney & Mia A. Rosenfeld & Taryn M. Lucas & Courtney M. Smith & Alice Li & Deniz Ince & Fiona L. Kearns & Alexandria S. Battison & Marie A, 2023. "Glycoproteomic landscape and structural dynamics of TIM family immune checkpoints enabled by mucinase SmE," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Juewon Kim & Yunju Jo & Donghyun Cho & Dongryeol Ryu, 2022. "L-threonine promotes healthspan by expediting ferritin-dependent ferroptosis inhibition in C. elegans," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    3. Víctor Taleb & Qinghua Liao & Yoshiki Narimatsu & Ana García-García & Ismael Compañón & Rafael Junqueira Borges & Andrés Manuel González-Ramírez & Francisco Corzana & Henrik Clausen & Carme Rovira & R, 2022. "Structural and mechanistic insights into the cleavage of clustered O-glycan patches-containing glycoproteins by mucinases of the human gut," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Itxaso Anso & Andreas Naegeli & Javier O. Cifuente & Ane Orrantia & Erica Andersson & Olatz Zenarruzabeitia & Alicia Moraleda-Montoya & Mikel García-Alija & Francisco Corzana & Rafael A. Orbe & Franci, 2023. "Turning universal O into rare Bombay type blood," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Bashar Shuoker & Michael J. Pichler & Chunsheng Jin & Hiroka Sakanaka & Haiyang Wu & Ana Martínez Gascueña & Jining Liu & Tine Sofie Nielsen & Jan Holgersson & Eva Nordberg Karlsson & Nathalie Juge & , 2023. "Sialidases and fucosidases of Akkermansia muciniphila are crucial for growth on mucin and nutrient sharing with mucus-associated gut bacteria," Nature Communications, Nature, vol. 14(1), pages 1-16, December.

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