Structural Aspects of Glycolipid Recognition of C-type Lectin Receptors in the Immune System

Abstract

Substances released from pathogens and damaged cells are specifically captured by various pattern recognition receptors in the host immune system. Of these it is the C-type lectin receptors (CLRs) whose function it is to recognize various types of ligands including glycans, glycolipids, lipids and proteins via small C-type lectin domains and to then transduce signals across the membrane. The released glycolipids are specifically recognized by various CLRs involved in the immune response. In this review, I briefly introduce structural aspects of the glycolipid recognition mechanisms of three CLRs involved in mycobacterial infection. These are Mincle, DCAR and Dectin-2. Mincle binds trehalose dimycolate and glycerol monomycolate which are cell wall components of mycobacteria, but it also binds to various (glyco)lipids such as β-glucosylceramide and cholesterol crystals derived from damaged cells. 3D structural analysis has revealed that Mincle has a sugar binding site that recognizes the trehalose disaccharide unit and a hydrophobic groove that accommodates the acyl chains. DCAR interacts with another mycobacterial glycolipid, phosphatidyl-myo-inositol mannoside. DCAR also accepts acyl chains via a hydrophobic groove, but it is situated in a very different position from that in Mincle. Dectin-2 binds mannose-capped lipoarabinomannan (Man-LAM), a glycolipid of pathogenic mycobacteria, via only the disaccharide unit, Manα1-2Man, and not the lipid moiety.