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The Active Site of ICP47, a Herpes Simplex Virus–encoded Inhibitor of the Major Histocompatibility Complex (MHC)-encoded Peptide Transporter Associated with Antigen Processing (TAP), Maps to the NH(2)-terminal 35 Residues

The herpes simplex virus (HSV) immediate early protein ICP47 inhibits the transporter associated with antigen processing (TAP)-dependent peptide translocation. As a consequence, empty major histocompatibility complex (MHC) class I molecules are retained in the endoplasmic reticulum and recognition o...

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Autores principales: Galocha, Begoña, Hill, Ann, Barnett, Barbara C., Dolan, Aidan, Raimondi, Alejandra, Cook, Richard F., Brunner, Joseph, McGeoch, Duncan J., Ploegh, Hidde L.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1997
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196299/
https://www.ncbi.nlm.nih.gov/pubmed/9151894
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author Galocha, Begoña
Hill, Ann
Barnett, Barbara C.
Dolan, Aidan
Raimondi, Alejandra
Cook, Richard F.
Brunner, Joseph
McGeoch, Duncan J.
Ploegh, Hidde L.
author_facet Galocha, Begoña
Hill, Ann
Barnett, Barbara C.
Dolan, Aidan
Raimondi, Alejandra
Cook, Richard F.
Brunner, Joseph
McGeoch, Duncan J.
Ploegh, Hidde L.
author_sort Galocha, Begoña
collection PubMed
description The herpes simplex virus (HSV) immediate early protein ICP47 inhibits the transporter associated with antigen processing (TAP)-dependent peptide translocation. As a consequence, empty major histocompatibility complex (MHC) class I molecules are retained in the endoplasmic reticulum and recognition of HSV-infected cells by cytotoxic T lymphocytes is abolished. We chemically synthesized full-length ICP47 (sICP47) and show that sICP47 inhibits TAP-dependent peptide translocation in human cells. Its biological activity is indistinguishable from that of recombinant ICP47 (rICP47). By using synthetic peptides, we mapped the core sequence of ICP47 minimally required for TAP inhibition to residues 2–35. This segment is located within the region of the molecule conserved between ICP47 from HSV-1 and HSV-2. Through alanine scanning substitution we identified three segments within this region that are critical for the ability to inhibit TAP function. The interaction of ICP47 with TAP is unlikely to mimic precisely that of the transported peptides, as deduced from differential labeling of the TAP1 and TAP2 subunits using sICP47 fragments with chemical cross-linkers.
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spelling pubmed-21962992008-04-16 The Active Site of ICP47, a Herpes Simplex Virus–encoded Inhibitor of the Major Histocompatibility Complex (MHC)-encoded Peptide Transporter Associated with Antigen Processing (TAP), Maps to the NH(2)-terminal 35 Residues Galocha, Begoña Hill, Ann Barnett, Barbara C. Dolan, Aidan Raimondi, Alejandra Cook, Richard F. Brunner, Joseph McGeoch, Duncan J. Ploegh, Hidde L. J Exp Med Article The herpes simplex virus (HSV) immediate early protein ICP47 inhibits the transporter associated with antigen processing (TAP)-dependent peptide translocation. As a consequence, empty major histocompatibility complex (MHC) class I molecules are retained in the endoplasmic reticulum and recognition of HSV-infected cells by cytotoxic T lymphocytes is abolished. We chemically synthesized full-length ICP47 (sICP47) and show that sICP47 inhibits TAP-dependent peptide translocation in human cells. Its biological activity is indistinguishable from that of recombinant ICP47 (rICP47). By using synthetic peptides, we mapped the core sequence of ICP47 minimally required for TAP inhibition to residues 2–35. This segment is located within the region of the molecule conserved between ICP47 from HSV-1 and HSV-2. Through alanine scanning substitution we identified three segments within this region that are critical for the ability to inhibit TAP function. The interaction of ICP47 with TAP is unlikely to mimic precisely that of the transported peptides, as deduced from differential labeling of the TAP1 and TAP2 subunits using sICP47 fragments with chemical cross-linkers. The Rockefeller University Press 1997-05-05 /pmc/articles/PMC2196299/ /pubmed/9151894 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Galocha, Begoña
Hill, Ann
Barnett, Barbara C.
Dolan, Aidan
Raimondi, Alejandra
Cook, Richard F.
Brunner, Joseph
McGeoch, Duncan J.
Ploegh, Hidde L.
The Active Site of ICP47, a Herpes Simplex Virus–encoded Inhibitor of the Major Histocompatibility Complex (MHC)-encoded Peptide Transporter Associated with Antigen Processing (TAP), Maps to the NH(2)-terminal 35 Residues
title The Active Site of ICP47, a Herpes Simplex Virus–encoded Inhibitor of the Major Histocompatibility Complex (MHC)-encoded Peptide Transporter Associated with Antigen Processing (TAP), Maps to the NH(2)-terminal 35 Residues
title_full The Active Site of ICP47, a Herpes Simplex Virus–encoded Inhibitor of the Major Histocompatibility Complex (MHC)-encoded Peptide Transporter Associated with Antigen Processing (TAP), Maps to the NH(2)-terminal 35 Residues
title_fullStr The Active Site of ICP47, a Herpes Simplex Virus–encoded Inhibitor of the Major Histocompatibility Complex (MHC)-encoded Peptide Transporter Associated with Antigen Processing (TAP), Maps to the NH(2)-terminal 35 Residues
title_full_unstemmed The Active Site of ICP47, a Herpes Simplex Virus–encoded Inhibitor of the Major Histocompatibility Complex (MHC)-encoded Peptide Transporter Associated with Antigen Processing (TAP), Maps to the NH(2)-terminal 35 Residues
title_short The Active Site of ICP47, a Herpes Simplex Virus–encoded Inhibitor of the Major Histocompatibility Complex (MHC)-encoded Peptide Transporter Associated with Antigen Processing (TAP), Maps to the NH(2)-terminal 35 Residues
title_sort active site of icp47, a herpes simplex virus–encoded inhibitor of the major histocompatibility complex (mhc)-encoded peptide transporter associated with antigen processing (tap), maps to the nh(2)-terminal 35 residues
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196299/
https://www.ncbi.nlm.nih.gov/pubmed/9151894
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