The active domain of the herpes simplex virus protein ICP47: A potent inhibitor of the transporter associated with antigen processing (TAP)
| Autor: | Lars Neumann, Robert Tampé, Stephan Uebel, Günther Jung, Wolfgang Kraas |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Recombinant Fusion Proteins
Molecular Sequence Data medicine.disease_cause Major histocompatibility complex Immediate-Early Proteins Major Histocompatibility Complex Mice Viral Proteins Immune system ATP Binding Cassette Transporter Subfamily B Member 3 Structural Biology MHC class I Escherichia coli medicine Animals Humans Simplexvirus Cytotoxic T cell Amino Acid Sequence ATP Binding Cassette Transporter Subfamily B Member 2 Amino Acids Molecular Biology Peptide sequence Binding Sites biology Endoplasmic reticulum Transporter associated with antigen processing Virology Cell biology Herpes simplex virus biology.protein ATP-Binding Cassette Transporters |
| Zdroj: | Journal of Molecular Biology. 272:484-492 |
| ISSN: | 0022-2836 |
| DOI: | 10.1006/jmbi.1997.1282 |
| Popis: | The herpes simplex virus type 1 (HSV-1) protein ICP47 binds specifically to the transporter associated with antigen processing (TAP), thereby blocking peptide-binding and translocation by TAP and subsequent loading of peptides onto MHC class I molecules in the endoplasmic reticulum. In consequence, HSV-infected cells are masked for immune recognition by cytotoxic T-lymphocytes. To investigate the molecular details of this, so far, unique transporter-inhibitor interaction, the active domain and critical amino acid residues were identified by using short overlapping fragments and systematic deletions of the viral inhibitor. A fragment of 32 amino acid residues, ICP47(3-34), was found to be the minimal region harboring an activity to inhibit peptide-binding to TAP comparable to the action of the full-length protein and therefore representing the active domain. Further N or C-terminal truncations cause an abrupt loss in activity. Within the identified active domain, various mutants and chimeras of ICP47 derived from HSV-1 and HSV-2 helped to identify amino acid residues critical for TAP inhibition. On the basis of these results, therapeutic drugs could be designed that are applicable in treatment of allograft rejection or in novel vaccination strategies against HSV, restoring the ability of the immune system to recognize HSV-infected cells. |
| Databáze: | OpenAIRE |
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