Antigen processing and presentation: TAPping into ABC transporters.
Adaptive, cell-mediated immunity involves the presentation of antigenic peptides on class I MHC molecules at the cell surface. This requires an ABC transporter associated with antigen processing (TAP) to transport antigenic peptides generated in the cytosol into the endoplasmic reticulum (ER) for loading onto class I MHC. Recent crystal structures of bacterial ABC transporters suggest how the transmembrane domains of TAP form a peptide-binding cavity that acquires peptides from the cytosol, and following ATP-induced conformational changes, the peptide-binding cavity closes to the cytosol and instead opens to the ER lumen for peptide release. Extensive biochemical studies show how transport is driven by ATP binding and hydrolysis on an asymmetric pair of cytosolic nucleotide-binding domains, which are physically coupled to the peptide-binding site to propagate conformational changes through the protein.
Procko
Erik
E
Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Gaudet
Rachelle
R
D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000276:immunology* / Q000378:metabolism; D000494:Allosteric Regulation / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000276:immunology*; D005786:Gene Expression Regulation; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D016056:Immunodominant Epitopes / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000276:immunology; D021381:Protein Transport
D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D010455:Peptides; C477327:transporter associated with antigen processing (TAP); D000255:Adenosine Triphosphate