Recognition of microbial glycans by soluble human lectins

Abstract

Human innate immune lectins that recognize microbial glycans can conduct microbial surveillance and thereby help prevent infection. Structural analysis of soluble lectins has provided invaluable insight into how these proteins recognize their cognate carbohydrate ligands and how this recognition gives rise to biological function. In this opinion, we cover the structural features of lectins that allow them to mediate microbial recognition, highlighting examples from the collectin, Reg protein, galectin, pentraxin, ficolin and intelectin families. These analyses reveal how some lectins (e.g., human intelectin-1) can recognize glycan epitopes that are remarkably diverse, yet still differentiate between mammalian and microbial glycans. We additionally discuss strategies to identify lectins that recognize microbial glycans and highlight tools that facilitate these discovery efforts.

Figure 1.

Structural representation of CRDs present in human soluble lectins. A) C-type lectin domain of rat MBL (PDB:2MSB) bound to oligosaccharide ligand [23]. B) C-type lectin domain of human RegIIIα (PDB:4MTH) with residues proposed to function in peptidoglycan binding highlighted in black [28••]. C) Beta-sandwich or jelly-roll fold from human galectin-3 (PDB:3ZSJ) bound to lactose [29]. D) Jelly-roll fold of human C-reactive protein bound to phosphorylcholine (PDB: 1B09) [30] E) Fibrinogen-like domain from human L-Ficolin bound to N-acetyl-glucosamine (PDB: 2J3U) [31]. F) Intelectin domain from human intelectin-1 bound to β-Galactofuranose (PDB: 4WMY) [16••]. G) Beta-prism fold from human ZG16p bound to mannose (PDB: 3VZF) [32]. Bound calcium ions are shown as green spheres and carbohydrate ligands are depicted in black.

Figure 2.

Lectin recognition of exocyclic 1,2-diols. A) Surface rendering of human intelectin-1 binding the exocyclic diol of allyl-β-D-Galf (PDB: 4WMY) [16]. The aromatic box in the ligand binding site, which is constrained by tryptophan 288 and tyrosine 297, is highlighted. B) Surface rendering of human SP-D binding the exocyclic diol of L-D-heptose (PDB: 2RIB) [27]. Calcium ions (green), oxygen atoms (red), and nitrogen atoms (blue) are highlighted. The protein-bound carbohydrate ligands are depicted in the stick representation.