title: The first N-terminal transmembrane helix of each subunit of the antigenic peptide transporter TAP is essential for independent tapasin binding.
abstract: The heterodimeric ABC transporter TAP translocates proteasomal degradation products from the cytosol into the lumen of the endoplasmic reticulum, where these peptides are loaded onto MHC class I molecules by a macromolecular peptide-loading complex (PLC) and subsequently shuttled to the cell surface for inspection by cytotoxic T lymphocytes. Tapasin recruits, as a central adapter protein, other components of the PLC at the unique N-terminal domains of TAP. We found that the N-terminal domains of human TAP1 and TAP2 can independently bind to tapasin, thus providing two separate loading platforms for PLC assembly. Moreover, tapasin binding is dependent on the first N-terminal transmembrane helix of TAP1 and TAP2, demonstrating that these two helices contribute independently to the recruitment of tapasin and associated factors.
authors.affiliation: Institute of Biochemistry, Biocenter, Johann Wolfgang Goethe-University Frankfurt, Marie-Curie Strasse 9, D-69439 Frankfurt a.M., Germany. joachim.koch@em.uni-frankfurt.de
authors.forename: Joachim
authors.initials: J
authors.lastname: Koch
authors.forename: Renate
authors.initials: R
authors.lastname: Guntrum
authors.forename: Robert
authors.initials: R
authors.lastname: Tampé
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D017920:Antiporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D026901:Membrane Transport Proteins; D010455:Peptides / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018411:Spodoptera / Q000166:cytology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D017920:Antiporters; D015395:Histocompatibility Antigens Class I; D007136:Immunoglobulins; D026901:Membrane Transport Proteins; D010455:Peptides; D011994:Recombinant Proteins; C107762:tapasin; C477327:transporter associated with antigen processing (TAP); D046988:Proteasome Endopeptidase Complex