T Cell Receptor Binding Transition States and Recognition of Peptide/MHC
| Autor: | Rebecca L. Davis-Harrison, Francis K. Insaidoo, Brian M. Baker |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Stereochemistry
Receptors Antigen T-Cell chemical and pharmacologic phenomena Peptide Major histocompatibility complex Biochemistry T cell receptor binding HLA-A2 Antigen Humans Receptor chemistry.chemical_classification biology Chemistry digestive oral and skin physiology T-cell receptor Models Immunological Surface Plasmon Resonance MHC restriction Transition state Kinetics Mutation Solvents biology.protein Biophysics Thermodynamics Protein folding Oligopeptides Algorithms |
| Zdroj: | Biochemistry. 46:1840-1850 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi061702p |
| Popis: | T cell receptor recognition of peptide/MHC has been described as proceeding through a "two-step" process in which the TCR first contacts the MHC molecule prior to formation of the binding transition state using the germline-encoded CDR1 and CDR2 loops. The receptor then contacts the peptide using the hypervariable CDR3 loops as the transition state decays to the bound state. The model subdivides TCR binding into peptide-independent and peptide-dependent steps, demarcated at the binding transition state. Investigating the two-step model, here we show that two TCRs that recognize the same peptide/MHC bury very similar amounts of solvent-accessible surface area in their transition states. However, 1300-1500 A2 of surface area is buried in each, a significant amount suggestive of participation of peptide and associated CDR3 surface. Consistent with this interpretation, analysis of peptide and TCR variants indicates that stabilizing contacts to the peptide are formed within both transition states. These data are incompatible with the original two-step model, as are transition state models built using the principle of minimal frustration commonly employed in the investigation of protein folding and binding transition states. These findings will be useful in further explorations of the nature of TCR binding transition states, as well as ongoing efforts to understand the mechanisms by which T cell receptors recognize the composite peptide/MHC surface. |
| Databáze: | OpenAIRE |
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