Transporter associated with antigen processing
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| transporter 1, ATP-binding cassette, sub-family B (MDR/TAP) | |
|---|---|
| Identifiers | |
| Symbol | TAP1 |
| Alt. symbols | ABCB2 |
| Entrez | 6890 |
| HUGO | 43 |
| OMIM | 170260 |
| RefSeq | NM_000593 |
| UniProt | Q03518 |
| Other data | |
| Locus | Chr. 6 p21.3 |
| transporter 2, ATP-binding cassette, sub-family B (MDR/TAP) | |
|---|---|
| Identifiers | |
| Symbol | TAP2 |
| Alt. symbols | ABCB3 |
| Entrez | 6891 |
| HUGO | 44 |
| OMIM | 170261 |
| RefSeq | NM_000544 |
| UniProt | Q03519 |
| Other data | |
| Locus | Chr. 6 p21.3 |
Transporter associated with antigen processing (TAP) protein complex belongs to the ATP-binding-cassette transporter family.[1] It delivers cytosolic peptides into the endoplasmic reticulum (ER), where they bind to nascent MHC class I molecules.[2]
The TAP structure is formed of two proteins: TAP-1 and TAP-2, which have one hydrophobic region and one ATP-binding region each. They assemble into a heterodimer, which results in a four-domain transporter.[3]
Function[edit | edit source]
The TAP transporter is found in the ER lumen associated with the peptide-loading complex (PLC). This complex of β2 microglobulin, calreticulin, ERp57, TAP, tapasin, and MHC class I acts to keep hold of MHC molecules until they have been fully loaded with peptides.[4]
Peptide transport[edit | edit source]
TAP-mediated peptide transport is a multistep process. The peptide-binding pocket is formed by TAP-1 and TAP-2. Association with TAP is an ATP-independent event, ‘in a fast bimolecular association step, peptide binds to TAP, followed by a slow isomerisation of the TAP complex’.[5] It is suggested that the conformational change in structure triggers ATP hydrolysis and so initiates peptide transport.[6]
Both nucleotide-binding domains (NBDs) are required for peptide translocation, as each NBD cannot hydrolyse ATP alone. The exact mechanism of transport is not known; however, findings indicate that ATP binding to TAP-1 is the initial step in the transport process, and that ATP bound to TAP-1 induces ATP binding in TAP-2. It has also been shown that undocking of the loaded MHC class I is linked to the transport cycle of TAP caused by signals from the TAP-1 subunit.[7]
Specificity[edit | edit source]
The ATPase activity of TAP is highly dependent on the presence of the correct substrate, and peptide binding is prerequisite for ATP hydrolysis. This prevents waste of ATP via peptide-independent hydrolysis.[6]
The specificity of TAP proteins was first investigated by trapping peptides in the ER using glycosylation. TAP binds to 8- to 16-residue peptides with equal affinity, while translocation is most efficient for peptides that are 8 to 12 residues long. Efficiency reduces for peptides longer than 12 residues.[8] However, peptides with more than 40 residues were translocated, albeit with low efficiency. Peptides with low affinity for the MHC class I molecule are transported out of the ER by an efficient ATP-dependent export protein. These outlined mechanisms may represent a mechanism for ensuring that only high-affinity peptides are bound to MHC class I.[9]
See also[edit | edit source]
References[edit | edit source]
- ↑ Daumke O, Knittler MR (2001). "Functional asymmetry of the ATP-binding-cassettes of the ABC transporter TAP is determined by intrinsic properties of the nucleotide binding domains". Eur. J. Biochem. 268 (17): 4776–86. doi:10.1046/j.1432-1327.2001.02406.x. PMID 11532014.
- ↑ Suh WK, Cohen-Doyle MF, Fruh K, Wang K, Peterson PA, Williams DB (1994). "Interaction of MHC class I molecules with the transporter associated with antigen processing". Science. 264 (5163): 1322–6. doi:10.1126/science.8191286. PMID 8191286.
- ↑ Janeway CA, Travers P, Walport M, Shlomchik M (2001). "Chapter 5, Antigen Presentation to T-lymphocytes". In Janeway, Charles. Immunobiology: the immune system in health and disease (5th ed.). New York: Garland. ISBN 0-8153-3642-X.
- ↑ Antoniou AN, Powis SJ, Elliott T (2003). "Assembly and export of MHC class I peptide ligands". Curr. Opin. Immunol. 15 (1): 75–81. doi:10.1016/S0952-7915(02)00010-9. PMID 12495737.
- ↑ van Endert PM, Tampé R, Meyer TH, Tisch R, Bach JF, McDevitt HO (1994). "A sequential model for peptide binding and transport by the transporters associated with antigen processing". Immunity. 1 (6): 491–500. doi:10.1016/1074-7613(94)90091-4. PMID 7895159.
- ↑ 6.0 6.1 Neumann L, Tampé R (1999). "Kinetic analysis of peptide binding to the TAP transport complex: evidence for structural rearrangements induced by substrate binding". J. Mol. Biol. 294 (5): 1203–13. doi:10.1006/jmbi.1999.3329. PMID 10600378.
- ↑ Alberts P, Daumke O, Deverson EV, Howard JC, Knittler MR (2001). "Distinct functional properties of the TAP subunits coordinate the nucleotide-dependent transport cycle". Curr. Biol. 11 (4): 242–51. doi:10.1016/S0960-9822(01)00073-2. PMID 11250152.
- ↑ Neefjes JJ, Momburg F, Hämmerling GJ (1993). "Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter". Science. 261 (5122): 769–71. doi:10.1126/science.8342042. PMID 8342042.
- ↑ Lankat-Buttgereit B, Tampé R (2002). "The transporter associated with antigen processing: function and implications in human diseases". Physiol. Rev. 82 (1): 187–204. doi:10.1152/physrev.00025.2001. PMID 11773612.
External links[edit | edit source]
- transporter+associated+with+antigen+processing+(TAP) at the US National Library of Medicine Medical Subject Headings (MeSH)
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