Antigenic peptides bind to major histocompatibility complex (MHC) molecules as a prerequisite for their presentation to T cells. In this study, we investigate possible structural preferences of MHC-binding peptides by examining the conformation space defined by the structures of these peptides within their native source proteins. Comparison of the conformation space of the native structures of MHC-binding nonamers and a corresponding conformation space defined by a random set of nonamers showed no significant difference. This suggests that the environment of the MHC binding groove has evolved to bind peptides with essentially any "structural background." A slight tendency for an extended β-conformation at positions 8 and 9 was observed for the set of native structures. We suggest that such a preference may facilitate the binding of the C-terminal anchor position of processed peptides into the corresponding specificity pocket. MHC-binding peptides represent examples of short subsequences that are present in two different structural environments: within their native protein and within the MHC binding groove. Comparison of the native and of the bound structure of the peptides showed that peptides up to 14 residues long may adopt different conformations within different protein environments. This has direct implications for structure prediction algorithms.
- Ligand binding
- MHC restriction
- Sequence - structure relationship
- Structural conservation
- T-cell immunity