TY - JOUR
T1 - Structural analysis for glycolipid recognition by the C-type lectins Mincle and MCL
AU - Furukawa, Atsushi
AU - Kamishikiryo, Jun
AU - Mori, Daiki
AU - Toyonaga, Kenji
AU - Okabe, Yuki
AU - Toji, Aya
AU - Kanda, Ryo
AU - Miyake, Yasunobu
AU - Ose, Toyoyuki
AU - Yamasaki, Sho
AU - Maenaka, Katsumi
PY - 2013/10/22
Y1 - 2013/10/22
N2 - 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 Ca 2+-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.
AB - 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 Ca 2+-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.
UR - http://www.scopus.com/inward/record.url?scp=84886424987&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84886424987&partnerID=8YFLogxK
U2 - 10.1073/pnas.1312649110
DO - 10.1073/pnas.1312649110
M3 - Article
C2 - 24101491
AN - SCOPUS:84886424987
VL - 110
SP - 17438
EP - 17443
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 43
ER -