title: Powering the peptide pump: TAP crosstalk with energetic nucleotides.
abstract: ATP-binding cassette (ABC) transporters represent a large family of membrane-spanning proteins that have a shared structural organization and conserved nucleotide-binding domains (NBDs). They transport a large variety of solutes, and defects in these transporters are an important cause of human disease. TAP (tmacr;ransporter associated with āntigen pmacr;rocessing) is a heterodimeric ABC transporter that uses nucleotides to drive peptide transport from the cytoplasm into the endoplasmic reticulum lumen, where the peptides then bind major histocompatibility complex (MHC) class I molecules. TAP plays an essential role in the MHC class I antigen presentation pathway. Recent studies show that the two NBDs of TAP fulfil distinct functions in the catalytic cycle of this transporter. In this opinion article, a model of alternating ATP binding and hydrolysis is proposed, in which nucleotide interaction with TAP2 primarily controls substrate binding and release, whereas interaction with TAP1 controls structural rearrangements of the transmembrane pathway. Viral proteins that inhibit TAP function cause arrests at distinct points of this catalytic cycle.
authors.affiliation: INSERM U25, Institut Necker, 161 rue de Sèvres, 75015 Paris, France. vanendert@necker.fr
authors.forename: Peter M
authors.initials: PM
authors.lastname: van Endert
authors.forename: Loredana
authors.initials: L
authors.lastname: Saveanu
authors.forename: Eric W
authors.initials: EW
authors.lastname: Hewitt
authors.forename: Paul
authors.initials: P
authors.lastname: Lehner
mesh_terms: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000737:chemistry / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000244:Adenosine Diphosphate / Q000378:metabolism / Q000502:physiology*; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D017951:Antigen Presentation; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D015235:HLA-B Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008285:Major Histocompatibility Complex; D018832:Molecular Chaperones / Q000276:immunology; D011487:Protein Conformation
chemical_list: D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D015235:HLA-B Antigens; D018832:Molecular Chaperones; C071692:TAP2 protein, human; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate