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Unraveling the role of the secretor antigen in human rotavirus attachment to histo-blood group antigens

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Unraveling the role of the secretor antigen in human rotavirus attachment to histo-blood group antigens

dc.contributor.author	Gozalbo Rovira, Roberto Vicente
dc.contributor.author	Ciges Tomas, José Rafael
dc.contributor.author	Vila Vicent, Susana
dc.contributor.author	Buesa Gómez, Javier
dc.contributor.author	Santiso Bellón, Cristina
dc.contributor.author	Monedero García, Vicente
dc.contributor.author	Yebra Yebra, María Jesús
dc.contributor.author	Marina Moreno, Alberto
dc.contributor.author	Rodríguez Díaz, Jesús
dc.date.accessioned	2020-06-10T08:02:19Z
dc.date.available	2020-06-10T08:02:19Z
dc.date.issued	2019
dc.identifier.citation	Gozalbo Rovira, Roberto Vicente Ciges Tomas, José Rafael Vila Vicent, Susana Buesa Gómez, Javier Santiso Bellón, Cristina Monedero García, Vicente Yebra Yebra, María Jesús Marina Moreno, Alberto Rodríguez Díaz, Jesús 2019 Unraveling the role of the secretor antigen in human rotavirus attachment to histo-blood group antigens PLOS pathogens 15 6 e1007865
dc.identifier.uri	https://hdl.handle.net/10550/74965
dc.description.abstract	Rotavirus is the leading agent causing acute gastroenteritis in young children, with the P[8] genotype accounting for more than 80% of infections in humans. The molecular bases for binding of the VP8* domain from P[8] VP4 spike protein to its cellular receptor, the secretory H type-1 antigen (Fuc-α1,2-Gal-β1,3-GlcNAc; H1), and to its precursor lacto-N-biose (Gal-β1,3-GlcNAc; LNB) have been determined. The resolution of P[8] VP8* crystal structures in complex with H1 antigen and LNB and site-directed mutagenesis experiments revealed that both glycans bind to the P[8] VP8* protein through a binding pocket shared with other members of the P[II] genogroup (i.e.: P[4], P[6] and P[19]). Our results show that the L-fucose moiety from H1 only displays indirect contacts with P[8] VP8. However, the induced conformational changes in the LNB moiety increase the ligand affinity by two-fold, as measured by surface plasmon resonance (SPR), providing a molecular explanation for the different susceptibility to rotavirus infection between secretor and non-secretor individuals. The unexpected interaction of P[8] VP8 with LNB, a building block of type-1 human milk oligosaccharides, resulted in inhibition of rotavirus infection, highlighting the role and possible application of this disaccharide as an antiviral. While key amino acids in the H1/LNB binding pocket were highly conserved in members of the P[II] genogroup, differences were found in ligand affinities among distinct P[8] genetic lineages. The variation in affinities were explained by subtle structural differences induced by amino acid changes in the vicinity of the binding pocket, providing a fine-tuning mechanism for glycan binding in P[8] rotavirus.
dc.language.iso	eng
dc.relation.ispartof	PLOS pathogens, 2019, vol. 15, num. 6, p. e1007865
dc.subject	Virus RNA
dc.subject	Gastroenterologia
dc.title	Unraveling the role of the secretor antigen in human rotavirus attachment to histo-blood group antigens
dc.type	journal article	es_ES
dc.date.updated	2020-06-10T08:02:31Z
dc.identifier.doi	10.1371/journal.ppat.1007865
dc.identifier.idgrec	133669
dc.rights.accessRights	open access	es_ES