BibTex format
@article{Feinberg:2021:10.1074/jbc.M116.749515,
author = {Feinberg, H and Rambaruth, ND and Jégouzo, SA and Jacobsen, KM and Djurhuus, R and Poulsen, TB and Weis, WI and Taylor, ME and Drickamer, K},
doi = {10.1074/jbc.M116.749515},
journal = {Journal of Biological Chemistry},
pages = {21222--21233},
title = {Binding sites for acylated trehalose analogs of glycolipid ligands on an extended carbohydrate-recognition domain of the macrophage receptor mincle},
url = {http://dx.doi.org/10.1074/jbc.M116.749515},
volume = {291},
year = {2021}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - The macrophage receptor mincle binds to trehalose dimycolate on the surface of Mycobacterium tuberculosis. Signaling initiated by this interaction leads to cytokine production, which underlies the ability of mycobacteria to evade the immune system and also to function as adjuvants. In previous work, the mechanism for binding of the sugar headgroup of trehalose dimycolate to mincle has been elucidated, but the basis for enhanced binding to glycolipid ligands, in which hydrophobic substituents are attached to the 6-hydroxyl groups, has been the subject of speculation. In the work reported here, the interaction of trehalose derivatives with bovine mincle has been probed with a series of synthetic mimics of trehalose dimycolate in binding assays, in structural studies by x-ray crystallography, and by site-directed mutagenesis. Binding studies reveal that, rather than reflecting specific structural preference, the apparent affinity of mincle for ligands with hydrophobic substituents correlates with their overall size. Structural and mutagenesis analysis provides evidence for interaction of the hydrophobic substituents with multiple different portions of the surface of mincle and confirms the presence of three Ca2+-binding sites. The structure of an extended portion of the extracellular domain of mincle, beyond the minimal C-type carbohydrate-recognition domain, also constrains the way that the binding domains may interact on the surface of macrophages.
AU - Feinberg,H
AU - Rambaruth,ND
AU - Jégouzo,SA
AU - Jacobsen,KM
AU - Djurhuus,R
AU - Poulsen,TB
AU - Weis,WI
AU - Taylor,ME
AU - Drickamer,K
DO - 10.1074/jbc.M116.749515
EP - 21233
PY - 2021///
SN - 1083-351X
SP - 21222
TI - Binding sites for acylated trehalose analogs of glycolipid ligands on an extended carbohydrate-recognition domain of the macrophage receptor mincle
T2 - Journal of Biological Chemistry
UR - http://dx.doi.org/10.1074/jbc.M116.749515
UR - https://www.sciencedirect.com/science/article/pii/S002192582035897X?via%3Dihub
UR - http://hdl.handle.net/10044/1/39559
VL - 291
ER -