ACCURACY OF A STRUCTURAL HOMOLOGY MODEL FOR A CLASS-II HISTOCOMPATIBILITY PROTEIN, HLA-DR1 - COMPARISON TO THE CRYSTAL-STRUCTURE

Structural homology modeling is used to test the accuracy by which a C lass I major histocompatibility complex (MHC) could be used to model a Class II MHC. The crystal structure of HLA-aw68 served as a reference molecule to model HLA-DR1. The resulting model was compared to the re cently released crystal structure by Brown et al. (Nature, Vol. 364, p . 33-39 (1993)). The overall tertiary structure motif(two alpha-helice s and a beta-sheet forming a peptide binding cleft) was maintained. Ho wever, significant deviations in the secondary structure elements were found between the model and the DR1 crystal structure. These deviatio ns were consistent with the differences between Class I and Class II c rystal structures. In regions where the model and DR1 crystal structur es are most similar, side chain orientations are also similar. Specifi c peptide-MHC interactions are discussed and compared with the crystal structure results.