Noncompetitive antibody neutralization of IL-10 revealed by protein engineering and X-ray crystallography

Academic Article


  • 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 Å 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.
  • Published In

  • Structure  Journal
  • Digital Object Identifier (doi)

    Author List

  • Josephson K; Jones BC; Walter LJ; DiGiacomo R; Indelicato SR; Walter MR
  • Start Page

  • 981
  • End Page

  • 987
  • Volume

  • 10
  • Issue

  • 7