|2z7x, resolution 2.10Å ()|
|Ligands:||, , , ,|
|Gene:||TLR2, TIL4, VLRB (Homo sapiens), TLR1, KIAA0012, VLRB (Homo sapiens)|
|Related:||2z80, 2z81, 2z82|
Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide
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.
Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide., Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO, Cell. 2007 Sep 21;130(6):1071-82. PMID:17889651
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
2z7x is a 3 chain structure with sequence from Homo sapiens. The November 2011 RCSB PDB Molecule of the Month feature on Toll-like Receptors by David Goodsell is 10.2210/rcsb_pdb/mom_2011_11. Full crystallographic information is available from OCA.