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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
Evolutionary ConservationCheck, 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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