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1lk3

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[[Image:1lk3.jpg|left|200px]]
[[Image:1lk3.jpg|left|200px]]
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{{Structure
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|GENE= IL10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])
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{{STRUCTURE_1lk3| PDB=1lk3 | SCENE= }}
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|RELATEDENTRY=[[1j7v|1J7V]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1lk3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1lk3 OCA], [http://www.ebi.ac.uk/pdbsum/1lk3 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1lk3 RCSB]</span>
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'''ENGINEERED HUMAN INTERLEUKIN-10 MONOMER COMPLEXED TO 9D7 FAB FRAGMENT'''
'''ENGINEERED HUMAN INTERLEUKIN-10 MONOMER COMPLEXED TO 9D7 FAB FRAGMENT'''
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[[Category: Walter, L J.]]
[[Category: Walter, L J.]]
[[Category: Walter, M R.]]
[[Category: Walter, M R.]]
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[[Category: antigen-antibody complex]]
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[[Category: Antigen-antibody complex]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 23:59:40 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:03:50 2008''
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Revision as of 20:59, 2 May 2008

Image:1lk3.jpg

Template:STRUCTURE 1lk3

ENGINEERED HUMAN INTERLEUKIN-10 MONOMER COMPLEXED TO 9D7 FAB FRAGMENT


Contents

Overview

IL-10 is a dimeric cytokine that must engage its high-affinity cell surface receptor, IL-10R1, to induce multiple cellular activities. Here we report the 1.9 A crystal structure of an engineered IL-10 monomer (IL-10M1) in complex with a neutralizing Fab fragment (9D7Fab). 9D7Fab and IL-10R1 bind distinct nonoverlapping surfaces on IL-10M1. Antagonism of the IL-10M1/IL-10R1 interaction is the result of 9D7Fab-induced conformational changes in the CD loop of IL-10M1 that indirectly alter the structure of the IL-10R1 binding site. A single mutation (Ile87Ala) in the same CD loop region of the Epstein-Barr virus IL-10 (ebvIL-10) also reduces IL-10R1 binding affinity, suggesting that ebvIL-10 and 9D7Fab use similar allosteric mechanisms to modulate IL-10R1 affinity and biological activity.

Disease

Known disease associated with this structure: Graft-versus-host disease, protection against OMIM:[124092], HIV-1, susceptibility to OMIM:[124092], Rheumatoid arthritis, progression of OMIM:[124092]

About this Structure

1LK3 is a Single protein structure of sequence from Homo sapiens and Rattus norvegicus. Full crystallographic information is available from OCA.

Reference

Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and x-ray crystallography., Josephson K, Jones BC, Walter LJ, DiGiacomo R, Indelicato SR, Walter MR, Structure. 2002 Jul;10(7):981-7. PMID:12121653 Page seeded by OCA on Fri May 2 23:59:40 2008

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