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- W2495604387 abstract "Since peptide-empty MHC class I molecules at the cell surface would be inefficient and probably dangerous for cells, class I molecules must select peptides with dissociation rates that are sufficiently slow to allow survival of the peptide-class I complex during the transit to the cell surface and for some time thereafter. Elliott and collaborators have shown that class I molecules, however, first bind low-affinity peptides in the ER and later exchange them for high-affinity ones before leaving for the Golgi apparatus (Williams et al., 2002). This process, termed peptide editing, depends on the class I - specific assembly factor, tapasin, which binds directly to class I molecules in the ER. How does tapasin work? Based on our molecular dynamics simulations (Zacharias and Springer, 2004), we hypothesize that it may bind to and deform the peptide binding site of class I molecules by moving one flexible helix away from the peptide. As a consequence, some of the hydrogen bonds between the class I molecule and the peptide backbone may break and reduce the affinity between peptide and class I molecule. This would lead to a rapid dissociation of low-affinity peptides from the class I molecule. As a conclusion, this hypothesis predicts that tapasin universally decreases the affinity of class I molecules for peptide ligands. Since it is difficult to recreate the entire class I loading complex with purified proteins (it contains several other chaperones), we are investigating peptide binding to class I molecules in the lumen of isolated microsomal membranes in the presence and absence of tapasin. Class I molecules are transcribed, translated, and translocated in vitro. Peptide is then added to the microsomes, and peptide-class I complexes are precipitated by conformation-specific antibodies. We have observed that tapasin mediates the binding of high-affinity peptide to MHC class I molecules in the ER by accelerating dissociation of low-affinity peptides." @default.
- W2495604387 created "2016-08-23" @default.
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- W2495604387 date "2009-08-12" @default.
- W2495604387 modified "2023-09-27" @default.
- W2495604387 title "The influence of tapasin on MHC class I-peptide interaction" @default.
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