PMID: 19119025

 

    Legend: Sugar

Title : Insights into MHC class I peptide loading from the structure of the tapasin- ERp57 thiol oxidoreductase heterodimer

Abstract :

1. Tapasin is a glycoprotein critical for loading major histocompatibility complex (MHC) class I molecules with high-affinity peptides
2. It functions within the multimeric peptide-loading complex ( PLC ) as a disulfide-linked, stable heterodimer with the thiol oxidoreductase ERp57 , and this covalent interaction is required to support optimal PLC activity
3. Here, we present the 2.6 A resolution structure of the tapasin- ERp57 core of the PLC
4. The structure revealed that tapasin interacts with both ERp57 catalytic domains , accounting for the stabil ity of th e hetero dimer, and provided an example of a protein disulfide isomerase family member interacting with substrate
5. Mutational analysis identified a conserved surface on tapasin that interacted with MHC class I molecules and was critical for peptide loading and editing functions of the tapasin- ERp57 heterodimer
6. By combining the tapasin- ERp57 structure with those of other defined PLC components, we present a molecular model that illuminates the processes involved in MHC class I peptide loading