title: Analysis of interactions in a tapasin/class I complex provides a mechanism for peptide selection.
abstract: We examined interactions in a soluble tapasin (TPN)/HLA-B*0801 complex to gain mechanistic insights into the functions of TPN. Results show that TPN acts as a chaperone by increasing the ratio of active-to-inactive peptide-deficient HLA-B*0801 molecules in solution. TPN causes peptides to associate and dissociate faster owing to its effect on widening the binding groove of HLA-B*0801 molecules. Our data indicate that a TPN-assisted mechanism of peptide selection relies on disruption of conserved hydrogen bonds at the C-terminal end of the groove. Peptide sequence-dependent interactions along the entire length of the groove also play a role in this mechanism. We suggest that TPN influences presentation of antigenic peptides according to a mechanistically complicated process in which bound candidate peptides that are unable to conformationally disengage TPN from class I molecules are excluded from the repertoire. Overall, these studies unify our understanding of the functions of TPN.
authors.affiliation: School of Pharmacy, University of Connecticut, Storrs, CT 06269, USA.
authors.forename: Mingnan
authors.initials: M
authors.lastname: Chen
authors.forename: Marlene
authors.initials: M
authors.lastname: Bouvier
mesh_terms: D017951:Antigen Presentation / Q000235:genetics / Q000502:physiology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D005454:Fluorescence Polarization; D015235:HLA-B Antigens / Q000378:metabolism*; D015795:HLA-B8 Antigen; D007700:Kinetics; D026901:Membrane Transport Proteins / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D017931:DNA Primers; D015235:HLA-B Antigens; C509422:HLA-B*08:01 antigen; D015795:HLA-B8 Antigen; D026901:Membrane Transport Proteins; D046912:Multiprotein Complexes; D010455:Peptides; C107762:tapasin