Snake venom galactoside-binding lectins: a structural and functional overview

Abstract

Snake venom galactoside-binding lectins (SVgalLs) comprise a class of toxins capable of recognizing and interacting with terminal galactoside residues of glycans. In the past 35 years, since the first report on the purification of thrombolectin from Bothrops atrox snake venom, several SVgalLs from Viperidae and Elapidae snake families have been described, as has progressive improvement in the investigation of structural/functional aspects of these lectins. Moreover, the advances of techniques applied in protein-carbohydrate recognition have provided important approaches in order to screen for possible biological targets. The present review describes the efforts over the past 35 years to elucidate SVgalLs, highlighting their structure and carbohydrate recognition function involved in envenomation pathophysiology and potential biomedical applications.

Keywords: Antitumor activity; Bactericidal activity; C-type lectin; Carbohydrate recognition domain; Galactoside-binding protein; Glycoconjugates; Inflammatory response; Mitogenic activity; Platelet aggregation; Snake venom.

Fig. 1

Multiple alignment of SVgalL. The multiple alignment was performed using the program Clustal-X, and sequence similarities using ESPript 3.0 [73] with structure prediction based on RSL structure [PDB: 1JZN]. Fully conserved residues are highlighted in red background. Cystein residues involved in the interchain disulfide link are indicated by green numbers. Carbohydrate recognition domain (CRD) is indicated by the blue box. Primary structure according to lectins: RSL [GI: 126130], ApL [GI: 510120659], BaL [GI: 34922645], CrL [GI: 118572769], BiL [GI: 82126834], BmLec [24], BpalL [GI: 527504051], BJcuL [25], BpirL [GI: 510120660], LmL [GI: 1881829], ToL [27] and TsL [GI: 7674107]

Fig. 2

RSL tertiary structure and carbohydrate binding site. RSL structure as described elsewhere [22]. a A cartoon representation of the RSL dimer complexed with lactose. Cysteine side and inter chains are shown in yellow, calcium and sodium ions are represented as red and orange circles, respectively, and lactose is shown in stick representation colored in red. b Cartoon representation of the carbohydrate-binding site interacting with lactose. c Oligomerization state with the decamer viewed down the pseudo-5-fold rotation axis. The 3D structure illustration was performed using the software Pymol (The PyMOL Molecular Graphics System, Version 1.5.0.4 Schrödinger, LLC.) from RSL entry [PDB: 1jzn]

Fig. 3

Glycan-recognition specificity. Top five glycan structures with highest binding recognition by the SVgalLs (a) RSL and (b) galatrox assessed by glycan microarray as described elsewhere [34, 42]