1ira
From Proteopedia
(New page: 200px<br /> <applet load="1ira" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ira, resolution 2.7Å" /> '''COMPLEX OF THE INTER...) |
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| - | [[Image:1ira.gif|left|200px]]<br /> | + | [[Image:1ira.gif|left|200px]]<br /><applet load="1ira" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1ira" size=" | + | |
caption="1ira, resolution 2.7Å" /> | caption="1ira, resolution 2.7Å" /> | ||
'''COMPLEX OF THE INTERLEUKIN-1 RECEPTOR WITH THE INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL1RA)'''<br /> | '''COMPLEX OF THE INTERLEUKIN-1 RECEPTOR WITH THE INTERLEUKIN-1 RECEPTOR ANTAGONIST (IL1RA)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Inflammation, regardless of whether it is provoked by infection or by | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1IRA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NAG as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1IRA is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NAG:'>NAG</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1IRA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Akeson, A.]] | [[Category: Akeson, A.]] | ||
| - | [[Category: Barrett, R | + | [[Category: Barrett, R W.]] |
[[Category: Bowlin, T.]] | [[Category: Bowlin, T.]] | ||
[[Category: Sarubbi, E.]] | [[Category: Sarubbi, E.]] | ||
| - | [[Category: Schreuder, H | + | [[Category: Schreuder, H A.]] |
[[Category: Soffientini, A.]] | [[Category: Soffientini, A.]] | ||
[[Category: Tardif, C.]] | [[Category: Tardif, C.]] | ||
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[[Category: receptor antagonist]] | [[Category: receptor antagonist]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:14:50 2008'' |
Revision as of 11:14, 21 February 2008
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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 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
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