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Dipeptides promote folding and peptide binding of MHC class I molecules.

ABSTRACT: MHC class I molecules bind only those peptides with high affinity that conform to stringent length and sequence requirements. We have now investigated which peptides can aid the in vitro folding of class I molecules, and we find that the dipeptide glycyl-leucine efficiently supports the folding of HLA-A*02:01 and H-2K(b) into a peptide-receptive conformation that rapidly binds high-affinity peptides. Treatment of cells with glycyl-leucine induces accumulation of peptide-receptive H-2K(b) and HLA-A*02:01 at the surface of cells. Other dipeptides with a hydrophobic second amino acid show similar enhancement effects. Our data suggest that the dipeptides bind into the F pocket like the C-terminal amino acids of a high-affinity peptide.

SUBMITTER: Saini SK

PROVIDER: S-EPMC3780906 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Dipeptides promote folding and peptide binding of MHC class I molecules.

Saini Sunil Kumar SK Ostermeir Katja K Ramnarayan Venkat Raman VR Schuster Heiko H Zacharias Martin M Springer Sebastian S

Proceedings of the National Academy of Sciences of the United States of America 20130903 38

MHC class I molecules bind only those peptides with high affinity that conform to stringent length and sequence requirements. We have now investigated which peptides can aid the in vitro folding of class I molecules, and we find that the dipeptide glycyl-leucine efficiently supports the folding of HLA-A*02:01 and H-2K(b) into a peptide-receptive conformation that rapidly binds high-affinity peptides. Treatment of cells with glycyl-leucine induces accumulation of peptide-receptive H-2K(b) and HLA ...[more]

PMID: 24003162

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