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Interaction of Glycolipids with the Macrophage Surface Receptor Mincle - a
Systematic Molecular Dynamics Study
#MMPMID29599490
Söldner CA
; Horn AHC
; Sticht H
Sci Rep
2018[Mar]; 8
(1
): 5374
PMID29599490
show ga
Synthetic analogues of mycobacterial trehalose-dimycolate such as trehalose acyl
esters have been proposed as novel adjuvants for vaccination. They induce an
immune response by binding to the macrophage C-type lectin receptor Mincle. The
binding site of trehalose is known, but there is yet only very limited structural
information about the binding mode of the acyl esters. Here, we performed a
systematic molecular dynamics study of trehalose mono-and diesters with different
chain lengths. All acyl chains investigated exhibited a high flexibility and
interacted almost exclusively with a hydrophobic groove on Mincle. Despite the
limited length of this hydrophobic groove, the distal parts of the longer
monoesters can still form additional interactions with this surface region due to
their conformational flexibility. In diesters, a certain length of the second
acyl chain is required to contact the hydrophobic groove. However, a stable
concomitant accommodation of both acyl chains in the groove is hampered by the
conformational rigidity of Mincle. Instead, multiple dynamic interaction modes
are observed, in which the second acyl chain contributes to binding. This
detailed structural information is considered helpful for the future design of
more affine ligands that may foster the development of novel adjuvants.
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