title: Tapasin edits peptides on MHC class I molecules by accelerating peptide exchange.
abstract: 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.
authors.affiliation: Biochemistry and Cell Biology, Jacobs University Bremen, Bremen, Germany.
authors.forename: P V K
authors.initials: PV
authors.lastname: Praveen
authors.forename: Rakina
authors.initials: R
authors.lastname: Yaneva
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.forename: Sebastian
authors.initials: S
authors.lastname: Springer
mesh_terms: 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
chemical_list: D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D010455:Peptides; C107762:tapasin