1ira | pdb_00001ira

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

spinqualitylabelsall models 1ira, resolution 2.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1ira is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.7Å Ligands: NAG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease IL1RA_HUMAN Genetic variation in IL1RN is associated with susceptibility to microvascular complications of diabetes type 4 (MVCD4) [MIM:612628. These are pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis. Defects in IL1RN are the cause of interleukin 1 receptor antagonist deficiency (DIRA) [MIM:612852; also known as deficiency of interleukin 1 receptor antagonist. Autoinflammatory diseases manifest inflammation without evidence of infection, high-titer autoantibodies, or autoreactive T-cells. DIRA is a rare, autosomal recessive, genetic autoinflammatory disease that results in sterile multifocal osteomyelitis (bone inflammation in multiple places), periostitis (inflammation of the membrane surrounding the bones), and pustulosis (due to skin inflammation) from birth. Function IL1RA_HUMAN Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Interleukin receptor 3D structures Interleukin receptor antagonist

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