1LK3

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

Summary for 1LK3

• Entry DOI: 10.2210/pdb1lk3/pdb
• Related: 1J7V
• Descriptor: Interleukin-10, 9D7 Light Chain, 9D7 Heavy Chain, ... (4 entities in total)
• Functional Keywords: antigen-antibody complex, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P22301
• Total number of polymer chains: 6
• Total formula weight: 129688.41

Authors

Josephson, K.,Jones, B.C.,Walter, L.J.,DiGiacomo, R.,Indelicato, S.R.,Walter, M.R. (deposition date: 2002-04-23, release date: 2002-07-17, Last modification date: 2024-11-13)

Primary citation

Josephson, K.,Jones, B.C.,Walter, L.J.,DiGiacomo, R.,Indelicato, S.R.,Walter, M.R.
Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and x-ray crystallography.
Structure, 10:981-987, 2002

PubMed Abstract: 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.

PubMed: 12121653
DOI: 10.1016/S0969-2126(02)00791-8

Experimental method

X-RAY DIFFRACTION (1.91 Å)