Structural highlights
Function
[CLC4D_HUMAN] Functions as an endocytic receptor. May be involved in antigen uptake at the site of infection, either for clearance of the antigen, or for processing and further presentation to T cells.[1]
Publication Abstract from PubMed
Mincle [macrophage inducible Ca2+-dependent (C-type) lectin; CLEC4E] and MCL (macrophage C-type lectin; CLEC4D) are receptors for the cord factor TDM (trehalose-6,6'-dimycolate), a unique glycolipid of mycobacterial cell-surface components, and activate immune cells to confer adjuvant activity. Although it is known that receptor-TDM interactions require both sugar and lipid moieties of TDM, the mechanisms of glycolipid recognition by Mincle and MCL remain unclear. We here report the crystal structures of Mincle, MCL, and the Mincle-citric acid complex. The structures revealed that these receptors are capable of interacting with sugar in a Ca2+-dependent manner, as observed in other C-type lectins. However, Mincle and MCL uniquely possess shallow hydrophobic regions found adjacent to their putative sugar binding sites, which reasonably locate for recognition of fatty acid moieties of glycolipids. Functional studies using mutant receptors as well as glycolipid ligands support this deduced binding mode. These results give insight into the molecular mechanism of glycolipid recognition through C-type lectin receptors, which may provide clues to rational design for effective adjuvants.
Structural analysis for glycolipid recognition by the C-type lectins Mincle and MCL.,Furukawa A, Kamishikiryo J, Mori D, Toyonaga K, Okabe Y, Toji A, Kanda R, Miyake Y, Ose T, Yamasaki S, Maenaka K Proc Natl Acad Sci U S A. 2013 Oct 7. PMID:24101491[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Arce I, Martinez-Munoz L, Roda-Navarro P, Fernandez-Ruiz E. The human C-type lectin CLECSF8 is a novel monocyte/macrophage endocytic receptor. Eur J Immunol. 2004 Jan;34(1):210-20. PMID:14971047 doi:http://dx.doi.org/10.1002/eji.200324230
- ↑ Furukawa A, Kamishikiryo J, Mori D, Toyonaga K, Okabe Y, Toji A, Kanda R, Miyake Y, Ose T, Yamasaki S, Maenaka K. Structural analysis for glycolipid recognition by the C-type lectins Mincle and MCL. Proc Natl Acad Sci U S A. 2013 Oct 7. PMID:24101491 doi:http://dx.doi.org/10.1073/pnas.1312649110