Structure of a classical MHC class I molecule that binds "non-classical" ligands


  • C.S. Hee
  • S. Gao
  • B. Loll
  • M.M. Miller
  • B. Uchanska-Ziegler
  • O. Daumke
  • A. Ziegler


  • PLoS Biology


  • PLoS Biol 8 (12): e1000557


  • Chicken YF1 genes share a close sequence relationship with classical MHC class I loci but map outside of the core MHC region. To obtain insights into their function, we determined the structure of the YF1*7.1/beta(2)-microgloblin complex by X-ray crystallography at 1.3 A resolution. It exhibits the architecture typical of classical MHC class I molecules but possesses a hydrophobic binding groove that contains a non-peptidic ligand. This finding prompted us to reconstitute YF1*7.1 also with various self-lipids. Seven additional YF1*7.1 structures were solved, but only polyethyleneglycol molecules could be modeled into the electron density within the binding groove. However, an assessment of YF1*7.1 by native isoelectric focusing indicated that the molecules were also able to bind nonself-lipids. The ability of YF1*7.1 to interact with hydrophobic ligands is unprecedented among classical MHC class I proteins and might aid the chicken immune system to recognize a diverse ligand repertoire with a minimal number of MHC class I molecules.