1G0Y

IL-1 RECEPTOR TYPE 1 COMPLEXED WITH ANTAGONIST PEPTIDE AF10847

Summary for 1G0Y

• Entry DOI: 10.2210/pdb1g0y/pdb
• Related: 1IRA 1ITB
• Descriptor: INTERLEUKIN-1 RECEPTOR, TYPE I, ANTAGONIST PEPTIDE AF10847 (2 entities in total)
• Functional Keywords: immunoglobulin, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane ; Single-pass type I membrane protein : P14778
• Total number of polymer chains: 2
• Total formula weight: 38515.60

Authors

Vigers, G.P.A.,Dripps, D.J.,Edwards, C.K.,Brandhuber, B.J. (deposition date: 2000-10-09, release date: 2000-10-25, Last modification date: 2024-10-30)

Primary citation

Vigers, G.P.,Dripps, D.J.,Edwards III, C.K.,Brandhuber, B.J.
X-ray crystal structure of a small antagonist peptide bound to interleukin-1 receptor type 1.
J.Biol.Chem., 275:36927-36933, 2000

PubMed Abstract: Interleukin (IL-1)alpha and IL-1beta are important mediators of inflammation. The binding of IL-1 to interleukin-1 receptor (IL-1R) type 1 is the initial step in IL-1 signal transduction and therefore is a tempting target for anti-inflammatory therapeutics. To advance our understanding of IL-1R1 binding interactions, we have determined the structure of the extracellular domains of IL-1R1 bound to a 21-amino acid IL-1 antagonist peptide at 3.0-A resolution. The antagonist peptide binds to the domain 1/2 junction of the receptor, which is a conserved binding site for IL-1beta and IL-1 receptor antagonist (IL-1ra). This co-crystal structure also reveals that considerable flexibility is present in IL-1R1 because the carboxyl-terminal domain of the receptor is rotated almost 170 degrees relative to the first two domains of the receptor compared with the previously solved IL-1R1.ligand structures. The structure shows an unexpected binding mode for the peptide and may contribute to the design of smaller IL-1R antagonists.

PubMed: 10903327
DOI: 10.1074/jbc.M006071200

Experimental method

X-RAY DIFFRACTION (3 Å)