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<table><tr><td colspan='2'>[[5u1d]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-1 Hhv-1] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U1D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U1D FirstGlance]. <br>
<table><tr><td colspan='2'>[[5u1d]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-1 Hhv-1] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U1D OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U1D FirstGlance]. <br>
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[[Category: Hhv-1]]
[[Category: Hhv-1]]
[[Category: Human]]
[[Category: Human]]
Revision as of 19:41, 6 March 2020
Cryo-EM structure of the human TAP ATP-Binding Cassette Transporter
5u1d is a 3 chain structure with sequence from Hhv-1 and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
[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] [TAP2_HUMAN] Immunodeficiency by defective expression of HLA class 1. The disease is caused by mutations affecting the gene represented in this entry.
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. [TAP2_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.
Publication Abstract from PubMed
The transporter associated with antigen processing (TAP) is an ATP-binding cassette (ABC) transporter essential to cellular immunity against viral infection. Some persistent viruses have evolved strategies to inhibit TAP so that they may go undetected by the immune system. The herpes simplex virus for example evades immune surveillance by blocking peptide transport with a small viral protein ICP47. In this study, we determined the structure of human TAP bound to ICP47 by electron cryo-microscopy (cryo-EM) to 4.0 A. The structure shows that ICP47 traps TAP in an inactive conformation distinct from the normal transport cycle. The specificity and potency of ICP47 inhibition result from contacts between the tip of the helical hairpin and the apex of the transmembrane cavity. This work provides a clear molecular description of immune evasion by a persistent virus. It also establishes the molecular structure of TAP to facilitate mechanistic studies of the antigen presentation process.
Structure of the transporter associated with antigen processing trapped by herpes simplex virus.,Oldham ML, Grigorieff N, Chen J Elife. 2016 Dec 9;5. pii: e21829. doi: 10.7554/eLife.21829. PMID:27935481[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
↑ Oldham ML, Grigorieff N, Chen J. Structure of the transporter associated with antigen processing trapped by herpes simplex virus. Elife. 2016 Dec 9;5. pii: e21829. doi: 10.7554/eLife.21829. PMID:27935481 doi:http://dx.doi.org/10.7554/eLife.21829
