The broad long-term objective of the proposed research is to understand the conformational changes in major histocompatibility complex (MHC) proteins and their role in antigen presentation.
The specific aims of the proposed research are to obtain structural information on empty and peptide-loaded forms of the human MHC protien, HLA-DR1, and to characterize the two empty forms of HLA-DR1 observed in kinetics experiments. Kinetics studies have indicated that the empty protein exists in two conformations in equilibrium: one peptide-receptive and one unable to bind peptide, peptide-averse. A mixture of these two conformations was previously used to characterize the difference between empty and peptide-loaded HLA-DR1. In the proposed research, I will determine the regions of HLA-DR1 that are responsible for the conformational change upon peptide binding with the use of NMR spectroscopy. Using a variety of bio-physical methods we will try to characterize differences between the peptide-receptive and peptide-averse forms of empty HLA-DR1. The health relatedness of this research is that the information, gathered will refine the current model for peptide binding of MHC class II and help in the development of synthetic peptides for potential use in disease treatment and in the identification of potential autoimmune antigens.
| Zavala-Ruiz, Zarixia; Strug, Iwona; Walker, Bruce D et al. (2004) A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition. Proc Natl Acad Sci U S A 101:13279-84 |
| Zavala-Ruiz, Zarixia; Strug, Iwona; Anderson, Matthew W et al. (2004) A polymorphic pocket at the P10 position contributes to peptide binding specificity in class II MHC proteins. Chem Biol 11:1395-402 |
| Zavala-Ruiz, Zarixia; Sundberg, Eric J; Stone, Jennifer D et al. (2003) Exploration of the P6/P7 region of the peptide-binding site of the human class II major histocompatability complex protein HLA-DR1. J Biol Chem 278:44904-12 |
