1ira
From Proteopedia
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|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ira FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ira OCA], [http://www.ebi.ac.uk/pdbsum/1ira PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ira RCSB]</span> | ||
}} | }} | ||
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==Overview== | ==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. | 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. | ||
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| - | ==Disease== | ||
| - | Known diseases associated with this structure: Gastric cancer risk after H. pylori infection OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147679 147679]], Mental retardation, X-linked, 21/34 OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=300206 300206]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Tramp-Kalmeyer, S.]] | [[Category: Tramp-Kalmeyer, S.]] | ||
[[Category: Yanofsky, S.]] | [[Category: Yanofsky, S.]] | ||
| - | [[Category: NAG]] | ||
[[Category: complex (cytokine receptor/antagonist)]] | [[Category: complex (cytokine receptor/antagonist)]] | ||
[[Category: cytokine receptor]] | [[Category: cytokine receptor]] | ||
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[[Category: receptor antagonist]] | [[Category: receptor antagonist]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 21:23:32 2008'' |
Revision as of 18:23, 30 March 2008
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| , resolution 2.7Å | |||||||
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| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
COMPLEX OF THE INTERLEUKIN-1 RECEPTOR WITH THE INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL1RA)
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.
About this Structure
1IRA is a Protein complex structure of sequences from Homo sapiens. 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 Sun Mar 30 21:23:32 2008
