title: Same structure, different function crystal structure of the Epstein-Barr virus IL-10 bound to the soluble IL-10R1 chain.
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 approximately 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 A 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.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Sung Il
authors.initials: SI
authors.lastname: Yoon
authors.forename: Brandi C
authors.initials: BC
authors.lastname: Jones
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Logsdon
authors.forename: Mark R
authors.initials: MR
authors.lastname: Walter
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002151:Calorimetry; D017931:DNA Primers; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation; D018123:Receptors, Interleukin / Q000378:metabolism*; D053701:Receptors, Interleukin-10; D017386:Sequence Homology, Amino Acid; D012995:Solubility
chemical_list: D017931:DNA Primers; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D016753:Interleukin-10