2Z81

Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide

Summary for 2Z81

• Entry DOI: 10.2210/pdb2z81/pdb
• Related: 2Z7X 2Z80 2Z82
• Descriptor: Toll-like receptor 2, Variable lymphocyte receptor B, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: tlr2, pam3csk4, lipopeptide, innate immunity, cytoplasmic vesicle, glycoprotein, immune response, inflammatory response, leucine-rich repeat, membrane, receptor, transmembrane, immune system
• Biological source: Mus musculus (house mouse, inshore hagfish); More
• Total number of polymer chains: 1
• Total formula weight: 64263.73

Authors

Lee, J.O.,Jin, M.S.,Kim, S.E.,Heo, J.Y. (deposition date: 2007-08-30, release date: 2007-10-02, Last modification date: 2023-11-01)

Primary citation

Jin, M.S.,Kim, S.E.,Heo, J.Y.,Lee, M.E.,Kim, H.M.,Paik, S.G.,Lee, H.,Lee, J.O.
Crystal Structure of the TLR1-TLR2 Heterodimer Induced by Binding of a Tri-Acylated Lipopeptide
Cell(Cambridge,Mass.), 130:1071-1082, 2007

PubMed 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.

PubMed: 17889651
DOI: 10.1016/j.cell.2007.09.008

Experimental method

X-RAY DIFFRACTION (1.8 Å)