title: 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.
authors.affiliation: Molecular Life Science Center, Jacobs University Bremen, 28759 Bremen, Germany.
authors.forename: Sunil Kumar
authors.initials: SK
authors.lastname: Saini
authors.forename: Katja
authors.initials: K
authors.lastname: Ostermeir
authors.forename: Venkat Raman
authors.initials: VR
authors.lastname: Ramnarayan
authors.forename: Heiko
authors.initials: H
authors.lastname: Schuster
authors.forename: Martin
authors.initials: M
authors.lastname: Zacharias
authors.forename: Sebastian
authors.initials: S
authors.lastname: Springer
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D004151:Dipeptides / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004926:Escherichia coli; D005434:Flow Cytometry; D005454:Fluorescence Polarization; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008856:Microscopy, Fluorescence; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D000596:Amino Acids; D004151:Dipeptides; D015789:HLA-A2 Antigen
keywords: antigen presentation; chemical chaperones; endoplasmic reticulum; ligand exchange; quality control