 |
PDBsum entry 3a7c
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Immune system
|
PDB id
|
|
|
|
3a7c
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Recognition of lipopeptide patterns by toll-Like receptor 2-Toll-Like receptor 6 heterodimer.
|
|
|
Authors
|
|
J.Y.Kang,
X.Nan,
M.S.Jin,
S.J.Youn,
Y.H.Ryu,
S.Mah,
S.H.Han,
H.Lee,
S.G.Paik,
J.O.Lee.
|
|
|
Ref.
|
|
Immunity, 2009,
31,
873-884.
|
|
|
PubMed id
|
|
|
|
|
|
|
|
|
Abstract
|
|
|
Toll-like receptor 2 (TLR2) initiates potent immune responses by recognizing
diacylated and triacylated lipopeptides. Its ligand specificity is controlled by
whether it heterodimerizes with TLR1 or TLR6. We have determined the crystal
structures of TLR2-TLR6-diacylated lipopeptide, TLR2-lipoteichoic acid, and
TLR2-PE-DTPA complexes. PE-DTPA,
1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-N-diethylenetriaminepentaacetic
acid, is a synthetic phospholipid derivative. Two major factors contribute to
the ligand specificity of TLR2-TLR1 or TLR2-TLR6 heterodimers. First, the lipid
channel of TLR6 is blocked by two phenylalanines. Simultaneous mutation of these
phenylalanines made TLR2-TLR6 fully responsive not only to diacylated but also
to triacylated lipopeptides. Second, the hydrophobic dimerization interface of
TLR2-TLR6 is increased by 80%, which compensates for the lack of amide lipid
interaction between the lipopeptide and TLR2-TLR6. The structures of the
TLR2-lipoteichoic acid and the TLR2-PE-DTPA complexes demonstrate that a precise
interaction pattern of the head group is essential for a robust immune response
by TLR2 heterodimers.
|
|
|
|
|
|
|
