Intracellular peptide transporters in human – compartmentalization of the “peptidome”

Abstract

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.

Alternative haplotypes of antigen processing genes in zebrafish diverged early in vertebrate evolution

“…Also found in jawless fish, such as lamprey (Fig. 5), the abcb9 gene in jawed vertebrates may have more limited function in MHCI antigen processing (41,42). The ancestral abcb9 gene is largely monomorphic, unlike the polymorphic tap1 and tap2 genes found in many jawed vertebrates.…”

Structure, Function, and Evolution of Bacterial ATP-Binding Cassette Systems

“…It is noteworthy that most eukaryotic IM-ABC transporters are specifically targeted to organelle membranes, which probably descend from a prokaryotic ancestor. For instance, the mammalian TAP protein, an IM-ABC exporter involved in the presentation of antigenic peptides to the class I major histocompatibility complex, is inserted into the endoplasmic reticulum (192). The ALD protein, putatively involved in the export of very-long-chain fatty acids from the cytosol into peroxisomes, is targeted to the peroxisomal membrane (515).…”

The Unfolded Protein Response (UPR)-activated Transcription Factor X-box-binding Protein 1 (XBP1) Induces MicroRNA-346 Expression That Targets the Human Antigen Peptide Transporter 1 (TAP1) mRNA and Governs Immune Regulatory Genes

“…The TAP1/TAP2 heterodimer translocates peptides, derived from the proteasomal degradation of cytosolic proteins, into the ER lumen (37)(38)(39)(40). These peptides are then loaded onto MHC class I molecules for subsequent presentation at the cell surface (41).…”