title: Pairing of the nucleotide binding domains of the transporter associated with antigen processing.
abstract: The transporter associated with antigen processing (TAP) comprises two structurally related subunits, TAP1 and TAP2, that form stable complexes in endoplasmic reticulum (ER) membranes. TAP complexes function in the translocation of peptides from the cytosol into the ER lumen for presentation by major histocompatibility complex class I molecules. Each TAP subunit contains an N-terminal membrane-spanning region with multiple membrane-spanning segments, and a C-terminal, cytosolic nucleotide binding region. To study the nature of the interactions occurring on the cytosolic face of TAP1/TAP2 complexes, we investigated quaternary associations mediated by two C-terminal fragments of human TAP1 (T1c, residues 452-748 and T1ctr, residues 472-748) and two C-terminal fragments of human TAP2 (T2c, residues 399-686 and T2ctr, residues 433-686). Each of these constructs contains the core nucleotide binding region as well as a long or short N-terminal extension. We show stable complex formation between T1c and T2c but not between T1ctr and T2ctr. The mechanistic implications of these results are discussed. We also show that each of the constructs except T1ctr interacts with wild type TAP1 and TAP2, indicating possibilities for homodimerization of TAP1 and TAP2, or of oligomerization of TAP1/TAP2 heterodimers on membranes.
authors.affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0620, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Lapinski
authors.forename: G G
authors.initials: GG
authors.lastname: Miller
authors.forename: R
authors.initials: R
authors.lastname: Tampé
authors.forename: M
authors.initials: M
authors.lastname: Raghavan
mesh_terms: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D017951:Antigen Presentation; D001665:Binding Sites; D019281:Dimerization; D006801:Humans; D009711:Nucleotides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011233:Precipitin Tests; D018411:Spodoptera
chemical_list: D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D009711:Nucleotides; D010446:Peptide Fragments; C073119:TAP1 protein, human; C071692:TAP2 protein, human; D000255:Adenosine Triphosphate