Same structure, different function: Crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10r1 chain

Academic Article

Abstract

  • Human IL-10 (hIL-10) is a cytokine that modulates diverse immune responses. The Epstein-Barr virus (EBV) genome contains an IL-10 homolog (vIL-10) that shares high sequence and structural similarity with hIL-10. Although vIL-10 suppresses inflammatory responses like hIL-10, it cannot activate many other immunostimulatory functions performed by the cellular cytokine. These functional differences have been correlated with the ∼1000-fold lower affinity of vIL-10, compared to hIL-10, for the IL-10R1 receptor chain. To define the structural basis for these observations, crystal structures of vIL-10 and a vIL-10 point mutant were determined bound to the soluble IL-10R1 receptor fragment (sIL-10R1) at 2.8 and 2.7 Å resolution, respectively. The structures reveal that subtle changes in the conformation and dynamics of the vIL-10 AB and CD loops and an orientation change of vIL-10 on sIL-10R1 are the main factors responsible for vIL-10's reduced affinity for sIL-10R1 and its distinct biological profile. ©2005 Elsevier Ltd. All rights reserved.
  • Published In

  • Structure  Journal
  • Digital Object Identifier (doi)

    Author List

  • Yoon SI; Jones BC; Logsdon NJ; Walter MR
  • Start Page

  • 551
  • End Page

  • 564
  • Volume

  • 13
  • Issue

  • 4