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ENGINEERED HUMAN INTERLEUKIN-10 MONOMER COMPLEXED TO 9D7 FAB FRAGMENTENGINEERED HUMAN INTERLEUKIN-10 MONOMER COMPLEXED TO 9D7 FAB FRAGMENT
Structural highlights
Function[IL10_HUMAN] Inhibits the synthesis of a number of cytokines, including IFN-gamma, IL-2, IL-3, TNF and GM-CSF produced by activated macrophages and by helper T-cells. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedIL-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. 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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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