| Autor: |
Rigney, Elizabeth, Kojima, Mayumi, Glithero, Ann, Elliott, Tim |
| Zdroj: |
Journal of Biological Chemistry; June 1998, Vol. 273 Issue: 23 p14200-14204, 5p |
| Abstrakt: |
Class I major histocompatibility complexes (MHC) are heterotrimeric structures comprising heavy chains (HC), β2-microglobulin (β2-m), and short antigenic peptides of 8–10 amino acids. These components assemble in the endoplasmic reticulum and are released to the cell surface only when a peptide of the appropriate length and sequence is incorporated into the structure. The binding of β2-m and peptide to HC is cooperative, and there is indirect evidence that the formation of a stable heterotrimer from an unstable HC:β2-m heterodimer involves a peptide-induced conformational change in the HC. Such a conformational change could ensure both a strong interaction between the three components and also signal the release of stably assembled class I MHC molecules from the endoplasmic reticulum. A peptide-induced conformational change in HC has been demonstrated in cell lysates lacking β2-m to which synthetic peptides were added. Many features of this conformational change suggest that it may be physiologically relevant. In an attempt to study the peptide-induced conformational change in detail we have expressed a soluble, truncated form of the mouse H-2DbHC that contains only the peptide binding domains of the class I molecule. We have shown that this peptide-binding “platform” is relatively stable in physiological buffers and undergoes a conformational change that is detectable with antibodies, in response to synthetic peptides. We also show that the structural features of peptides that induce this conformational change in the platform are the same as those required to observe the conformational change in full-length HC. In this respect, therefore, the HC α1and α2domains, which together form the peptide binding site of class I MHC, are able to act independently of the rest of the molecule. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
|
