1IRA

COMPLEX OF THE INTERLEUKIN-1 RECEPTOR WITH THE INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL1RA)

Summary for 1IRA

• Entry DOI: 10.2210/pdb1ira/pdb
• Descriptor: INTERLEUKIN-1 RECEPTOR ANTAGONIST, INTERLEUKIN-1 RECEPTOR, 2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total)
• Functional Keywords: cytokine receptor, receptor antagonist, immunoglobulin fold, complex (cytokine receptor-antagonist), complex (cytokine receptor-antagonist) complex, complex (cytokine receptor/antagonist)
• Biological source: Homo sapiens (human); More
• Cellular location: Isoform 1: Secreted. Isoform 2: Cytoplasm. Isoform 3: Cytoplasm. Isoform 4: Cytoplasm: P18510; Membrane ; Single-pass type I membrane protein : P14778
• Total number of polymer chains: 2
• Total formula weight: 54771.97

Authors

Schreuder, H.A.,Tardif, C.,Tramp-Kalmeyer, S.,Soffientini, A.,Sarubbi, E.,Akeson, A.,Bowlin, T.,Yanofsky, S.,Barrett, R.W. (deposition date: 1998-04-09, release date: 1998-06-17, Last modification date: 2023-08-09)

Primary citation

Schreuder, H.,Tardif, C.,Trump-Kallmeyer, S.,Soffientini, A.,Sarubbi, E.,Akeson, A.,Bowlin, T.,Yanofsky, S.,Barrett, R.W.
A new cytokine-receptor binding mode revealed by the crystal structure of the IL-1 receptor with an antagonist.
Nature, 386:194-200, 1997

PubMed Abstract: Inflammation, regardless of whether it is provoked by infection or by tissue damage, starts with the activation of macrophages which initiate a cascade of inflammatory responses by producing the cytokines interleukin-1 (IL-1) and tumour necrosis factor-alpha (ref. 1). Three naturally occurring ligands for the IL-1 receptor (IL1R) exist: the agonists IL-1alpha and IL-1beta and the IL-1-receptor antagonist IL1RA (ref. 2). IL-1 is the only cytokine for which a naturally occurring antagonist is known. Here we describe the crystal structure at 2.7 A resolution of the soluble extracellular part of type-I IL1R complexed with IL1RA. The receptor consists of three immunoglobulin-like domains. Domains 1 and 2 are tightly linked, but domain three is completely separate and connected by a flexible linker. Residues of all three domains contact the antagonist and include the five critical IL1RA residues which were identified by site-directed mutagenesis. A region that is important for biological function in IL-1beta, the 'receptor trigger site' is not in direct contact with the receptor in the IL1RA complex. Modelling studies suggest that this IL-1beta trigger site might induce a movement of domain 3.

PubMed: 9062194
DOI: 10.1038/386194a0

Experimental method

X-RAY DIFFRACTION (2.7 Å)