# Structural basis for carbohydrate recognition by the Gal/GalNAc lectin of Entamoeba histolytica involved in host cell adhesion

## TL;DR

This study reveals the structure of a key protein in the deadly parasite Entamoeba histolytica, which helps it bind to human cells and cause disease.

## Contribution

The first structural characterization of the Gal/GalNAc lectin and its sugar-binding mechanism in Entamoeba histolytica.

## Key findings

- The Gal/GalNAc lectin's sugar-binding site is located in the light chain with a β-trefoil fold.
- The heavy chain forms an elongated arm that adopts multiple positions, possibly modulated by sugar binding.

## 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 obtained in the presence of ligand show that the Gal/GalNAc binding site is in the light chain, which adopts a β-trefoil fold found in other lectins. An elongated arm emerges from the heavy chain, which adopts multiple positions and may be modulated by sugar binding. This study reveals the molecular basis for sugar binding by the Entamoeba histolytica Gal/GalNAc lectin, a prerequisite for parasite invasion and development of intestinal disease.

Entamoeba histolytica is the second most deadly eukaryotic parasite to affect humans. It causes amoebiasis, a disease in which the parasite induces dysentery and diarrhoea. If untreated, the infection can then develop into tissue damage, with the amoeba inducing abscesses in tissues such as the liver. These are caused when it ‘bites’ bits off our cells, through a process known as trogocytosis. An important molecular complex lies at the centre of this pathology. A lectin is found on the surface of the amoeba, which binds to carbohydrate-containing molecules on the surfaces of our cells. These interactions are required for the amoeba to attack our tissues and vaccination with parts of the lectin can prevent tissue damage. In this study, we show for the first time what this lectin looks like and how it recognises carbohydrates. We also show that the lectin contains an extended lever arm, which can adopt multiple positions relative to the ordered core. Future studies will reveal what the lever arm does and how antibodies against it prevent killing of our cells. In the meantime, this first view of the lectin shows us how this deadly amoeba recognises our cells and will guide vaccine development.