1ira
From Proteopedia
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COMPLEX OF THE INTERLEUKIN-1 RECEPTOR WITH THE INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL1RA)
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Gastric cancer risk after H. pylori infection OMIM:[147679], Mental retardation, X-linked, 21/34 OMIM:[300206]
About this Structure
1IRA is a Protein complex structure of sequences from Homo sapiens with NAG as ligand. Full crystallographic information is available from OCA.
Reference
A new cytokine-receptor binding mode revealed by the crystal structure of the IL-1 receptor with an antagonist., Schreuder H, Tardif C, Trump-Kallmeyer S, Soffientini A, Sarubbi E, Akeson A, Bowlin T, Yanofsky S, Barrett RW, Nature. 1997 Mar 13;386(6621):194-200. PMID:9062194
Page seeded by OCA on Mon Nov 12 17:33:43 2007
