Transporter associated with antigen processing

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transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
Symbol TAP1
Alt. symbols ABCB2
Entrez 6890
OMIM 170260
RefSeq NM_000593
UniProt Q03518
Other data
Locus Chr. 6 p21.3
transporter 2, ATP-binding cassette, sub-family B (MDR/TAP)
Symbol TAP2
Alt. symbols ABCB3
Entrez 6891
OMIM 170261
RefSeq NM_000544
UniProt Q03519
Other data
Locus Chr. 6 p21.3

Transporter associated with antigen processing (TAP) is a member of 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]


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]

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]


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]


  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ 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. ^ a b 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. 
  7. ^ 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. 
  8. ^ 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. 
  9. ^ 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. 

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