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| | <StructureSection load='1jj7' size='340' side='right'caption='[[1jj7]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='1jj7' size='340' side='right'caption='[[1jj7]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1jj7]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JJ7 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1JJ7 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1jj7]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JJ7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JJ7 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.4Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TAP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1jj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jj7 OCA], [http://pdbe.org/1jj7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1jj7 RCSB], [http://www.ebi.ac.uk/pdbsum/1jj7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1jj7 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1jj7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jj7 OCA], [https://pdbe.org/1jj7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jj7 RCSB], [https://www.ebi.ac.uk/pdbsum/1jj7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jj7 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/TAP1_HUMAN TAP1_HUMAN]] Defects in TAP1 are a cause of bare lymphocyte syndrome type 1 (BLS1) [MIM:[http://omim.org/entry/604571 604571]]; also called HLA class I deficiency. BLS1 is a class I antigen deficiency that is not accompanied by particular pathologic manifestations during the first years of life. Systemic infections have not been described. Chronic bacterial infections, often beginning in the first decade of life, are restricted to the respiratory tract.<ref>PMID:10074494</ref> | + | [https://www.uniprot.org/uniprot/TAP1_HUMAN TAP1_HUMAN] Defects in TAP1 are a cause of bare lymphocyte syndrome type 1 (BLS1) [MIM:[https://omim.org/entry/604571 604571]; also called HLA class I deficiency. BLS1 is a class I antigen deficiency that is not accompanied by particular pathologic manifestations during the first years of life. Systemic infections have not been described. Chronic bacterial infections, often beginning in the first decade of life, are restricted to the respiratory tract.<ref>PMID:10074494</ref> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TAP1_HUMAN TAP1_HUMAN]] Involved in the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class I molecules. Also acts as a molecular scaffold for the final stage of MHC class I folding, namely the binding of peptide. Nascent MHC class I molecules associate with TAP via tapasin. Inhibited by the covalent attachment of herpes simplex virus ICP47 protein, which blocks the peptide-binding site of TAP. Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of the TAP complex and inhibits peptide translocation by specifically blocking ATP-binding to TAP1 and prevents the conformational rearrangement of TAP induced by peptide binding. Inhibited by human adenovirus E3-19K glycoprotein, which binds the TAP complex and acts as a tapasin inhibitor, preventing MHC class I/TAP association. Expression of TAP1 is down-regulated by human Epstein-Barr virus vIL-10 protein, thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules. | + | [https://www.uniprot.org/uniprot/TAP1_HUMAN TAP1_HUMAN] Involved in the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class I molecules. Also acts as a molecular scaffold for the final stage of MHC class I folding, namely the binding of peptide. Nascent MHC class I molecules associate with TAP via tapasin. Inhibited by the covalent attachment of herpes simplex virus ICP47 protein, which blocks the peptide-binding site of TAP. Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of the TAP complex and inhibits peptide translocation by specifically blocking ATP-binding to TAP1 and prevents the conformational rearrangement of TAP induced by peptide binding. Inhibited by human adenovirus E3-19K glycoprotein, which binds the TAP complex and acts as a tapasin inhibitor, preventing MHC class I/TAP association. Expression of TAP1 is down-regulated by human Epstein-Barr virus vIL-10 protein, thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Gaudet, R]] | + | [[Category: Gaudet R]] |
| - | [[Category: Wiley, D C]] | + | [[Category: Wiley DC]] |
| - | [[Category: Abc atpase domain]]
| + | |
| - | [[Category: Helical domain]]
| + | |
| - | [[Category: P-loop]]
| + | |
| - | [[Category: Protein transport]]
| + | |
| Structural highlights
Disease
TAP1_HUMAN Defects in TAP1 are a cause of bare lymphocyte syndrome type 1 (BLS1) [MIM:604571; also called HLA class I deficiency. BLS1 is a class I antigen deficiency that is not accompanied by particular pathologic manifestations during the first years of life. Systemic infections have not been described. Chronic bacterial infections, often beginning in the first decade of life, are restricted to the respiratory tract.[1]
Function
TAP1_HUMAN Involved in the transport of antigens from the cytoplasm to the endoplasmic reticulum for association with MHC class I molecules. Also acts as a molecular scaffold for the final stage of MHC class I folding, namely the binding of peptide. Nascent MHC class I molecules associate with TAP via tapasin. Inhibited by the covalent attachment of herpes simplex virus ICP47 protein, which blocks the peptide-binding site of TAP. Inhibited by human cytomegalovirus US6 glycoprotein, which binds to the lumenal side of the TAP complex and inhibits peptide translocation by specifically blocking ATP-binding to TAP1 and prevents the conformational rearrangement of TAP induced by peptide binding. Inhibited by human adenovirus E3-19K glycoprotein, which binds the TAP complex and acts as a tapasin inhibitor, preventing MHC class I/TAP association. Expression of TAP1 is down-regulated by human Epstein-Barr virus vIL-10 protein, thereby affecting the transport of peptides into the endoplasmic reticulum and subsequent peptide loading by MHC class I molecules.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The transporter associated with antigen processing (TAP) is an ABC transporter formed of two subunits, TAP1 and TAP2, each of which has an N-terminal membrane-spanning domain and a C-terminal ABC ATPase domain. We report the structure of the C-terminal ABC ATPase domain of TAP1 (cTAP1) bound to ADP. cTAP1 forms an L-shaped molecule with two domains, a RecA-like domain and a small alpha-helical domain. The diphosphate group of ADP interacts with the P-loop as expected. Residues thought to be involved in gamma-phosphate binding and hydrolysis show flexibility in the ADP-bound state as evidenced by their high B-factors. Comparisons of cTAP1 with other ABC ATPases from the ABC transporter family as well as ABC ATPases involved in DNA maintenance and repair reveal key regions and residues specific to each family. Three ATPase subfamilies are identified which have distinct adenosine recognition motifs, as well as distinct subdomains that may be specific to the different functions of each subfamily. Differences between TAP1 and TAP2 in the nucleotide-binding site may be related to the observed asymmetry during peptide transport.
Structure of the ABC ATPase domain of human TAP1, the transporter associated with antigen processing.,Gaudet R, Wiley DC EMBO J. 2001 Sep 3;20(17):4964-72. PMID:11532960[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Furukawa H, Murata S, Yabe T, Shimbara N, Keicho N, Kashiwase K, Watanabe K, Ishikawa Y, Akaza T, Tadokoro K, Tohma S, Inoue T, Tokunaga K, Yamamoto K, Tanaka K, Juji T. Splice acceptor site mutation of the transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome. J Clin Invest. 1999 Mar;103(5):755-8. PMID:10074494 doi:10.1172/JCI5335
- ↑ Gaudet R, Wiley DC. Structure of the ABC ATPase domain of human TAP1, the transporter associated with antigen processing. EMBO J. 2001 Sep 3;20(17):4964-72. PMID:11532960 doi:10.1093/emboj/20.17.4964
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