A highly conserved sequence of the viral TAP inhibitor ICP47 is required for freezing of the peptide transport cycle.
Average rating
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Matschulla, TonyBerry, Richard
Gerke, Carolin
Döring, Marius
Busch, Julia
Paijo, Jennifer
Kalinke, Ulrich
Momburg, Frank
Hengel, Hartmut
Halenius, Anne
Issue Date
2017-06-07
Metadata
Show full item recordAbstract
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.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 RepAffiliation
TWINCORE, Zentrum für experimentelle und klinische Infectionsforschung GmbH, Feodor-Lynen-Str. 7, 30625 Hannover, Germany.Journal
Scientific reportsPubMed ID
28592828Type
ArticleLanguage
enISSN
2045-2322ae974a485f413a2113503eed53cd6c53
10.1038/s41598-017-02994-5
Scopus Count
The following license files are associated with this item:
- Creative Commons
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
Related articles
- 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 NH2-terminal 35 residues.
- Authors: Galocha B, Hill A, Barnett BC, Dolan A, Raimondi A, Cook RF, Brunner J, McGeoch DJ, Ploegh HL
- Issue date: 1997 May 5
- Molecular mechanism and species specificity of TAP inhibition by herpes simplex virus ICP47.
- Authors: Ahn K, Meyer TH, Uebel S, Sempé P, Djaballah H, Yang Y, Peterson PA, Früh K, Tampé R
- Issue date: 1996 Jul 1
- Structure of the viral TAP-inhibitor ICP47 induced by membrane association.
- Authors: Beinert D, Neumann L, Uebel S, Tampé R
- Issue date: 1997 Apr 15
- The active domain of the herpes simplex virus protein ICP47: a potent inhibitor of the transporter associated with antigen processing.
- Authors: Neumann L, Kraas W, Uebel S, Jung G, Tampé R
- Issue date: 1997 Oct 3
- Stable binding of the herpes simplex virus ICP47 protein to the peptide binding site of TAP.
- Authors: Tomazin R, Hill AB, Jugovic P, York I, van Endert P, Ploegh HL, Andrews DW, Johnson DC
- Issue date: 1996 Jul 1