Empty class II major histocompatibility complex created by peptide photolysis establishes the role of DM in peptide association
| Autor: | Maxine Yang, Arup K. Chakraborty, Kai W. Wucherpfennig, Kathrin Wilbuer, Gijsbert M. Grotenbreg, Melissa J. Nicholson, Leah M. Octavio, Kevin D. Fowler, Hidde L. Ploegh |
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| Rok vydání: | 2007 |
| Předmět: |
Time Factors
Light Stereochemistry Photochemistry Ultraviolet Rays Peptide Plasma protein binding Major histocompatibility complex Biochemistry Models Biological Article Major Histocompatibility Complex MHC class I Humans Molecular Biology HLA-D Antigens chemistry.chemical_classification Photolysis biology Histocompatibility Antigens Class II Cell Biology MHC restriction Models Theoretical Receptor–ligand kinetics Kinetics chemistry Models Chemical biology.protein Peptides Fluorescence anisotropy Protein Binding |
| Zdroj: | The Journal of biological chemistry. 282(29) |
| ISSN: | 0021-9258 |
| Popis: | DM catalyzes the exchange of peptides bound to Class II major histocompatibility complex (MHC) molecules. Because the dissociation and association components of the overall reaction are difficult to separate, a detailed mechanism of DM catalysis has long resisted elucidation. UV irradiation of DR molecules loaded with a photocleavable peptide (caged Class II MHC molecules) enabled synchronous and verifiable evacuation of the peptide-binding groove and tracking of early binding events in real time by fluorescence polarization. Empty DR molecules generated by photocleavage rapidly bound peptide but quickly resolved into species with substantially slower binding kinetics. DM formed a complex with empty DR molecules that bound peptide with even faster kinetics than empty DR molecules just having lost their peptide cargo. Mathematical models demonstrate that the peptide association rate of DR molecules is substantially higher in the presence of DM. We therefore unequivocally establish that DM contributes directly to peptide association through formation of a peptide-loading complex between DM and empty Class II MHC. This complex rapidly acquires a peptide analogous to the MHC class I peptide-loading complex. |
| Databáze: | OpenAIRE |
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