Tapasin edits peptides on MHC class I molecules by accelerating peptide exchange.
The endoplasmic reticulum (ER) protein tapasin is essential for the loading of high-affinity peptides onto MHC class I molecules. It mediates peptide editing, i.e. the binding of peptides of successively higher affinity until class I molecules pass ER quality control and exit to the cell surface. The molecular mechanism of action of tapasin is unknown. We describe here the reconstitution of tapasin-mediated peptide editing on class I molecules in the lumen of microsomal membranes. We find that in a competitive situation between high- and low-affinity peptides, tapasin mediates the binding of the high-affinity peptide to class I by accelerating the dissociation of the peptide from an unstable intermediate of the binding reaction.
Praveen
P V K
PV
Biochemistry and Cell Biology, Jacobs University Bremen, Bremen, Germany.
Yaneva
Rakina
R
Kalbacher
Hubert
H
Springer
Sebastian
S
D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000276:immunology*; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding
D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin