Intracellular peptide transporters in human--compartmentalization of the "peptidome".
In the human genome, the five adenosine triphosphate (ATP)-binding cassette (ABC) half transporters ABCB2 (TAP1), ABCB3 (TAP2), ABCB9 (TAP-like), and in part, also ABCB8 and ABCB10 are closely related with regard to their structural and functional properties. Although targeted to different cellular compartments such as the endoplasmic reticulum (ER), lysosomes, and mitochondria, they are involved in intracellular peptide trafficking across membranes. The transporter associated with antigen processing (TAP1 and TAP2) constitute a key machinery in the major histocompatibility complex (MHC) class I-mediated cellular immune defense against infected or malignantly transformed cells. TAP translocates the cellular "peptidome" derived primarily from cytosolic proteasomal degradation into the ER lumen for presentation by MHC class I molecules. The homodimeric ABCB9 (TAP-like) complex located in lysosomal compartments shares structural and functional similarities to TAP; however, its biological role seems to be different from the MHC I antigen processing. ABCB8 and ABCB10 are targeted to the inner mitochondrial membrane. MDL1, the yeast homologue of ABCB10, is involved in the export of peptides derived from proteolysis of inner-membrane proteins into the intermembrane space. As such peptides are presented as minor histocompatibility antigens on the surface of mammalian cells, a physiological role of ABCB10 in the antigen processing can be accounted.
Herget
Meike
M
Institute of Biochemistry, Biocenter, Goethe-University Frankfurt, Frankfurt, Germany.
Tampé
Robert
R
D064286:ATP Binding Cassette Transporter 1; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology; D017951:Antigen Presentation; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D008247:Lysosomes / Q000502:physiology; D008954:Models, Biological; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000502:physiology; D013379:Substrate Specificity; D014764:Viral Proteins / Q000502:physiology
C412459:ABCB10 protein, human; C412573:ABCB9 protein, human; D064286:ATP Binding Cassette Transporter 1; D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; C105843:ICP47 protein, Herpes simplex virus; D017874:Immediate-Early Proteins; D016601:RNA-Binding Proteins; C073119:TAP1 protein, human; C432877:US6 protein, Human cytomegalovirus; D014764:Viral Proteins; C071692:TAP2 protein, human