A highly conserved sequence of the viral TAP inhibitor ICP47 is required for freezing of the peptide transport cycle.

2.50
Hdl Handle:
http://hdl.handle.net/10033/620997
Title:
A highly conserved sequence of the viral TAP inhibitor ICP47 is required for freezing of the peptide transport cycle.
Authors:
Matschulla, Tony; Berry, Richard; Gerke, Carolin; Döring, Marius; Busch, Julia; Paijo, Jennifer; Kalinke, Ulrich; Momburg, Frank; Hengel, Hartmut; Halenius, Anne
Abstract:
The transporter associated with antigen processing (TAP) translocates antigenic peptides into the endoplasmic reticulum (ER) lumen for loading onto MHC class I molecules. This is a key step in the control of viral infections through CD8+ T-cells. The herpes simplex virus type-1 encodes an 88 amino acid long species-specific TAP inhibitor, ICP47, that functions as a high affinity competitor for the peptide binding site on TAP. It has previously been suggested that the inhibitory function of ICP47 resides within the N-terminal region (residues 1-35). Here we show that mutation of the highly conserved 50PLL52 motif within the central region of ICP47 attenuates its inhibitory capacity. Taking advantage of the human cytomegalovirus-encoded TAP inhibitor US6 as a luminal sensor for conformational changes of TAP, we demonstrated that the 50PLL52 motif is essential for freezing of the TAP conformation. Moreover, hierarchical functional interaction sites on TAP dependent on 50PLL52 could be defined using a comprehensive set of human-rat TAP chimeras. This data broadens our understanding of the molecular mechanism underpinning TAP inhibition by ICP47, to include the 50PLL52 sequence as a stabilizer that tethers the TAP-ICP47 complex in an inward-facing conformation.
Affiliation:
TWINCORE, Zentrum für experimentelle und klinische Infectionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.
Citation:
A highly conserved sequence of the viral TAP inhibitor ICP47 is required for freezing of the peptide transport cycle. 2017, 7 (1):2933 Sci Rep
Journal:
Scientific reports
Issue Date:
7-Jun-2017
URI:
http://hdl.handle.net/10033/620997
DOI:
10.1038/s41598-017-02994-5
PubMed ID:
28592828
Type:
Article
Language:
en
ISSN:
2045-2322
Appears in Collections:
publications of the department of experimental infection research ([TC] EXPI)

Full metadata record

DC FieldValue Language
dc.contributor.authorMatschulla, Tonyen
dc.contributor.authorBerry, Richarden
dc.contributor.authorGerke, Carolinen
dc.contributor.authorDöring, Mariusen
dc.contributor.authorBusch, Juliaen
dc.contributor.authorPaijo, Jenniferen
dc.contributor.authorKalinke, Ulrichen
dc.contributor.authorMomburg, Franken
dc.contributor.authorHengel, Hartmuten
dc.contributor.authorHalenius, Anneen
dc.date.accessioned2017-07-05T14:25:58Z-
dc.date.available2017-07-05T14:25:58Z-
dc.date.issued2017-06-07-
dc.identifier.citationA highly conserved sequence of the viral TAP inhibitor ICP47 is required for freezing of the peptide transport cycle. 2017, 7 (1):2933 Sci Repen
dc.identifier.issn2045-2322-
dc.identifier.pmid28592828-
dc.identifier.doi10.1038/s41598-017-02994-5-
dc.identifier.urihttp://hdl.handle.net/10033/620997-
dc.description.abstractThe transporter associated with antigen processing (TAP) translocates antigenic peptides into the endoplasmic reticulum (ER) lumen for loading onto MHC class I molecules. This is a key step in the control of viral infections through CD8+ T-cells. The herpes simplex virus type-1 encodes an 88 amino acid long species-specific TAP inhibitor, ICP47, that functions as a high affinity competitor for the peptide binding site on TAP. It has previously been suggested that the inhibitory function of ICP47 resides within the N-terminal region (residues 1-35). Here we show that mutation of the highly conserved 50PLL52 motif within the central region of ICP47 attenuates its inhibitory capacity. Taking advantage of the human cytomegalovirus-encoded TAP inhibitor US6 as a luminal sensor for conformational changes of TAP, we demonstrated that the 50PLL52 motif is essential for freezing of the TAP conformation. Moreover, hierarchical functional interaction sites on TAP dependent on 50PLL52 could be defined using a comprehensive set of human-rat TAP chimeras. This data broadens our understanding of the molecular mechanism underpinning TAP inhibition by ICP47, to include the 50PLL52 sequence as a stabilizer that tethers the TAP-ICP47 complex in an inward-facing conformation.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titleA highly conserved sequence of the viral TAP inhibitor ICP47 is required for freezing of the peptide transport cycle.en
dc.typeArticleen
dc.contributor.departmentTWINCORE, Zentrum für experimentelle und klinische Infectionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.en
dc.identifier.journalScientific reportsen

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