The first N-terminal transmembrane helix of each subunit of the antigenic peptide transporter TAP is essential for independent tapasin binding.
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.
Koch
Joachim
J
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
Guntrum
Renate
R
Tampé
Robert
R
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
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