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bioRxiv · 10.1101/2024.08.28.610168

Structural basis for carbohydrate recognition by the Gal/GalNAc lectin of Entamoeba histolytica

Gerard, S. F.·Redfield, C.·Higgins, M. K.
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Abstract

Intestinal amoebiasis is caused by Entamoeba histolytica, one of the deadliest human-infective parasites. Central to its pathogenicity is its binding to mucosal carbohydrates, which precedes tissue damage by trogocytosis. Carbohydrate binding is mediated by a single adhesin, the galactose/N-acetylgalactosamine (Gal/GalNAc) lectin, which is the leading vaccine candidate for amoebiasis. We present the structure of the native heterodimeric lectin, revealing an ordered core containing the light chain and the N-terminal region of the heavy chain. Structures in the presence of ligand show that the Gal/GalNAc binding site is in the light chain. An elongated arm emerges from the heavy chain, which adopts multiple positions. This arm contains the epitope for a monoclonal antibody which blocks binding to target cells, located unexpectedly away from the Gal/GalNAc binding site. This study reveals the molecular basis for sugar binding by the Entamoeba histolytica Gal/GalNAc lectin and will guide future vaccine development against amoebiasis.

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Gerard, S. F., Redfield, C., Higgins, M. K.. 2024-08-29. Structural basis for carbohydrate recognition by the Gal/GalNAc lectin of Entamoeba histolytica. https://doi.org/10.1101/2024.08.28.610168

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