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1lk3
From Proteopedia
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==Overview== | ==Overview== | ||
| - | IL-10 is a dimeric cytokine that must engage its high-affinity cell | + | 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== | ==Disease== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: DiGiacomo, R.]] | [[Category: DiGiacomo, R.]] | ||
| - | [[Category: Indelicato, S | + | [[Category: Indelicato, S R.]] |
| - | [[Category: Jones, B | + | [[Category: Jones, B C.]] |
[[Category: Josephson, K.]] | [[Category: Josephson, K.]] | ||
| - | [[Category: Walter, L | + | [[Category: Walter, L J.]] |
| - | [[Category: Walter, M | + | [[Category: Walter, M R.]] |
[[Category: antigen-antibody complex]] | [[Category: antigen-antibody complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:45:43 2008'' |
Revision as of 11:45, 21 February 2008
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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 diseases 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 Thu Feb 21 13:45:43 2008
