Transporter associated with antigen processing

Transporter associated with antigen processing

protein
Name=transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)
caption=


width=
HGNCid=43
Symbol=TAP1
AltSymbols=ABCB2
EntrezGene=6890
OMIM=170260
RefSeq=NM_000593
UniProt=Q03518
PDB=
ECnumber=
Chromosome=6
Arm=p
Band=21.3
LocusSupplementaryData=
protein
Name=transporter 2, ATP-binding cassette, sub-family B (MDR/TAP)
caption=


width=
HGNCid=44
Symbol=TAP2
AltSymbols=ABCB3
EntrezGene=6891
OMIM=170261
RefSeq=NM_000544
UniProt=Q03519
PDB=
ECnumber=
Chromosome=6
Arm=p
Band=21.3
LocusSupplementaryData=

Transporter associated with antigen processing (TAP) is a member of the ATP-binding-cassette transporter family.cite journal | author = Daumke O, Knittler MR | title = Functional asymmetry of the ATP-binding-cassettes of the ABC transporter TAP is determined by intrinsic properties of the nucleotide binding domains | journal = Eur. J. Biochem. | volume = 268 | issue = 17 | pages = 4776–86 | year = 2001 | pmid = 11532014 | doi = 10.1046/j.1432-1327.2001.02406.x | issn = ] It delivers cytosolic peptides into the endoplasmic reticulum (ER), where they bind to nascent MHC class I molecules.cite journal | author = Suh WK, Cohen-Doyle MF, Fruh K, Wang K, Peterson PA, Williams DB | title = Interaction of MHC class I molecules with the transporter associated with antigen processing | journal = Science | volume = 264 | issue = 5163 | pages = 1322–6 | year = 1994 | pmid = 8191286 | doi = | url = http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=8191286 | issn = ]

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.cite book | editor = Janeway, Charles | author = Janeway CA, Travers P, Walport M and Shlomchik M | title = Immunobiology: the immune system in health and disease | edition = 5th Ed. | publisher = Garland | location = New York | year = 2001 | pages = | isbn = 0-8153-3642-X | oclc = | doi = | chapter = Chapter 5, Antigen Presentation to T-lymphocytes]

Function

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.cite journal | author = Antoniou AN, Powis SJ, Elliott T | title = Assembly and export of MHC class I peptide ligands | journal = Curr. Opin. Immunol. | volume = 15 | issue = 1 | pages = 75–81 | year = 2003 | pmid = 12495737 | doi = 10.1016/S0952-7915(02)00010-9 | issn = ]

Peptide transport

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’.cite journal | author = van Endert PM, Tampé R, Meyer TH, Tisch R, Bach JF, McDevitt HO | title = A sequential model for peptide binding and transport by the transporters associated with antigen processing | journal = Immunity | volume = 1 | issue = 6 | pages = 491–500 | year = 1994 | pmid = 7895159 | doi = 10.1016/1074-7613(94)90091-4 | issn = ] It is suggested that the conformational change in structure triggers ATP hydrolysis and so initiates peptide transport.cite journal | author = Neumann L, Tampé R | title = Kinetic analysis of peptide binding to the TAP transport complex: evidence for structural rearrangements induced by substrate binding | journal = J. Mol. Biol. | volume = 294 | issue = 5 | pages = 1203–13 | year = 1999 | pmid = 10600378 | doi = 10.1006/jmbi.1999.3329 | issn = ]

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.cite journal | author = Alberts P, Daumke O, Deverson EV, Howard JC, Knittler MR | title = Distinct functional properties of the TAP subunits coordinate the nucleotide-dependent transport cycle | journal = Curr. Biol. | volume = 11 | issue = 4 | pages = 242–51 | year = 2001 | pmid = 11250152 | doi = 10.1016/S0960-9822(01)00073-2 | issn = ]

pecificity

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.cite journal | author = Neumann L, Tampé R | title = Kinetic analysis of peptide binding to the TAP transport complex: evidence for structural rearrangements induced by substrate binding | journal = J. Mol. Biol. | volume = 294 | issue = 5 | pages = 1203–13 | year = 1999 | pmid = 10600378 | doi = 10.1006/jmbi.1999.3329 | issn = ]

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.cite journal | author = Neefjes JJ, Momburg F, Hämmerling GJ | title = Selective and ATP-dependent translocation of peptides by the MHC-encoded transporter | journal = Science | volume = 261 | issue = 5122 | pages = 769–71 | year = 1993 | pmid = 8342042 | doi = | url = http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=8342042 | issn = ] 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.cite journal | author = Lankat-Buttgereit B, Tampé R | title = The transporter associated with antigen processing: function and implications in human diseases | journal = Physiol. Rev. | volume = 82 | issue = 1 | pages = 187–204 | year = 2002 | pmid = 11773612 | doi = 10.1152/physrev.00025.2001 | issn = ]

ee also

*Endoplasmic Reticulum
*MHC Class I
*Immune System

References

External links

*


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