Transporter associated with antigen processing

2018-11-07T03:08:25Z

2405:204:1400:C712:0:0:2785:40B1:

{{infobox protein
|Name=[[hAP1|transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)]]
|caption=
|image=
|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=
}}
{{infobox protein
|Name=[[TAP2|transporter 2, ATP-binding cassette, sub-family B (MDR/TAP)]]
|caption=
|image=
|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''') [[protein complex]] belongs to the [[ATP-binding cassette transporter|ATP-binding-cassette transporter family]].<ref name="pmid11532014">{{cite journal |vauthors=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 }}</ref> It delivers cytosolic peptides into the [[endoplasmic reticulum]] (ER), where they bind to nascent [[MHC class I]] molecules.<ref name="pmid8191286">{{cite journal |vauthors=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 = 10.1126/science.8191286| url = http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=8191286 }}</ref>

The TAP structure is formed of two proteins: [[TAP1|TAP-1]] and [[TAP2|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.<ref name="isbn0-8153-3642-X">{{cite book | editor = Janeway, Charles |vauthors=Janeway CA, Travers P, Walport M, Shlomchik M | title = Immunobiology: the immune system in health and disease | edition = 5th | publisher = Garland | location = New York | year = 2001 | pages = | isbn = 0-8153-3642-X | oclc = | doi = | chapter = Chapter 5, Antigen Presentation to T-lymphocytes}}</ref>

==Function==

The TAP transporter is found in the ER lumen associated with the ''[[peptide-loading complex]]'' (PLC). This complex of [[Beta-2 microglobulin|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.<ref name="pmid12495737">{{cite journal |vauthors=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 }}</ref>

===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’.<ref name="pmid7895159">{{cite journal |vauthors=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 }}</ref> It is suggested that the conformational change in structure triggers ATP hydrolysis and so initiates peptide transport.<ref name="pmid10600378">{{cite journal |vauthors=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 }}</ref>

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.<ref name="pmid11250152">{{cite journal |vauthors=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 }}</ref>

===Specificity===
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.<ref name="pmid10600378" />

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.<ref name="pmid8342042">{{cite journal |vauthors=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 = 10.1126/science.8342042| url = http://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=8342042 }}</ref> 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.<ref name="pmid11773612">{{cite journal |vauthors=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 }}</ref>

==See also==
*[[Endoplasmic Reticulum]]
*[[MHC Class I]]
*[[Immune System]]

==References==
{{Reflist|2}}

==External links==
* {{MeshName|transporter+associated+with+antigen+processing+(TAP)}}

{{ABC transporters}}

[[Category:ABC transporters]]
[[Category:Immune system]]

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Transporter associated with antigen processing