2Z80: Crystal Structure Of The Tlr1-tlr2 Heterodimer Induced By Binding Of A Tri-acylated Lipopeptide

Citation:
Abstract
TLR2 in association with TLR1 or TLR6 plays an important role in the innate immune response by recognizing microbial lipoproteins and lipopeptides. Here we present the crystal structures of the human TLR1-TLR2-lipopeptide complex and of the mouse TLR2-lipopeptide complex. Binding of the tri-acylated lipopeptide, Pam(3)CSK(4), induced the formation of an "m" shaped heterodimer of the TLR1 and TLR2 ectodomains whereas binding of the di-acylated lipopeptide, Pam(2)CSK(4), did not. The three lipid chains of Pam(3)CSK(4) mediate the heterodimerization of the receptor; the two ester-bound lipid chains are inserted into a pocket in TLR2, while the amide-bound lipid chain is inserted into a hydrophobic channel in TLR1. An extensive hydrogen-bonding network, as well as hydrophobic interactions, between TLR1 and TLR2 further stabilize the heterodimer. We propose that formation of the TLR1-TLR2 heterodimer brings the intracellular TIR domains close to each other to promote dimerization and initiate signaling.
PDB ID: 2Z80Download
MMDB ID: 59995
PDB Deposition Date: 2007/8/30
Updated in MMDB: 2012/10
Experimental Method:
x-ray diffraction
Resolution: 1.8  Å
Similar Structures:
Biological Unit for 2Z80: monomeric; determined by software (PISA)
Molecular Components in 2Z80
Label Count Molecule
Protein (1 molecule)
1
Toll-like Receptor 2, Variable Lymphocyte Receptor B(Gene symbol: TLR2)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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