Structure and Function of C-type Lectin Receptors

We have focused on members of the C-type lectin family, which are expressed on cells of the innate immune system. These cell surface receptors promote pathogen recognition and, in some cases, also endocytosis. This recognition process is based on the interaction of the lectins with glycans found on the invading pathogen, often sufficient avidity is gained by homooligomerization of the receptor. On a molecular level, a central Ca²⁺ located in the carbohydrate binding site allows for the coordination of the glycan. Once endocytosed, this Ca²⁺ coordination can be perturbed by endosomal acidification and reduction of local Ca²⁺ concentration. While Ca²⁺ sequestering directly impairs carbohydrate recognition, pH-dependent loss of the receptor multimerization state results indirectly in cargo release in the endo-/lysosomal pathway. Taken together, C-type lectins harbor several molecular determinants in their overall architecture to promote pathogen binding, but also to enhance cargo release, rendering these receptors rather flexible on various time scales.