1lk3
From Proteopedia
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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
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