Members of a novel protein family containing MAR domains act as sialic acid-binding lectins during host cell invasion by apicomplexan parasites

Friedrich, Nikolas; Santos, Joana M.; Liu, Yan; Palma, Angelina S.; Leon, Ester; Kiso, Makoto; Blackman, Michael J.; Matthews, Stephen; Feizi, Ten; Soldati-Favre, Dominique

doi:10.1074/jbc.M109.060988

Scientific article

English

Members of a novel protein family containing MAR domains act as sialic acid-binding lectins during host cell invasion by apicomplexan parasites

Contributors

Friedrich, Nikolas; Santos, Joana M.; Liu, Yan; Palma, Angelina S.; Leon, Ester; Kiso, Makoto; Blackman, Michael J.; Matthews, Stephen; Feizi, Ten; Soldati-Favre, Dominique

Published in

The Journal of biological chemistry, vol. 285, no. 3, p. 2064-2076

Publication date

2010

Abstract

Numerous intracellular pathogens exploit cell surface glycoconjugates for host cell recognition and entry. Unlike bacteria and viruses, Toxoplasma gondii and other parasites of the phylum Apicomplexa actively invade host cells and this process critically depends on adhesins (MICs) released onto the parasite surface from intracellular organelles called micronemes. The microneme adhesive repeat (MAR) domain of T. gondii MIC1 (TgMIC1) recognizes sialic acid (Sia), a key determinant on the host-cell surface for invasion by this pathogen. By complementation and invasion assays, we demonstrate that TgMIC1 is one important player in Sia-dependent invasion, and that another novel Sia-binding lectin, designated TgMIC13, is also involved. Using BLAST searches, we identify a family of MAR-containing proteins in enteroparasitic coccidians, a subclass of apicomplexans including T. gondii, suggesting that all these parasites exploit sialylated glycoconjugates on host-cells as determinants for enteric invasion. Furthermore this protein family might provide a basis for the broad host-cell range observed for coccidians that form tissue cysts during chronic infection. Carbohydrate microarray analyses, corroborated by structural considerations, show that TgMIC13, TgMIC1 and its homologue Neospora caninum MIC1 (NcMIC1) share a preference for alpha2-3- over alpha2-6-linked sialyl-N-acetyllactosamine sequences. However, the three lectins also display differences in binding preferences. Intense binding of TgMIC13 to alpha2-9-linked disialyl-sequence reported on embryonal cells and relatively strong binding to 4-O-acetylated-Sia found on gut epithelium, and binding of NcMIC1 to 6'sulpho-sialyl Lewis(x) might have implications for tissue tropism.

UNIGE affiliation entities

Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire

UNIGE research groups

Biologie d'un parasite intracellulaire obligatoire (773)

Citation (ISO format)

FRIEDRICH, Nikolas et al. Members of a novel protein family containing MAR domains act as sialic acid-binding lectins during host cell invasion by apicomplexan parasites. In: The Journal of biological chemistry, 2010, vol. 285, n° 3, p. 2064–2076. doi: 10.1074/jbc.M109.060988

Article (Published version)

Supplemental data - III

Supplemental data - V

Supplemental data - II

Identifiers

PID : unige:4720
DOI : 10.1074/jbc.M109.060988
PMID : 19901027

Additional URL for this publication

http://www.jbc.org/content/285/3/2064.long

Journal ISSN

0021-9258

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Creation

11/01/2010 12:16:00

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11/01/2010 12:16:00

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14/03/2023 15:19:50

Status update

14/03/2023 15:19:49

Last indexation

29/10/2024 12:49:26

Members of a novel protein family containing MAR domains act as sialic acid-binding lectins during host cell invasion by apicomplexan parasites

Contributors

Published in

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Abstract

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UNIGE research groups

Citation (ISO format)

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Additional URL for this publication

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Technical informations

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First validation

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Status update

Last indexation