Evidence map›Paper›PMID 27845362›Full record

ArticleScientific reports2016

A dual inhibition mechanism of herpesviral ICP47 arresting a conformationally thermostable TAP complex.

Valentina Herbring, Anja Bäucker, Simon Trowitzsch, Robert Tampé

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.9field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Herpes Simplex Virus Evasion of Early Host Antiviral Responses.Frontiers in cellular and infection microbiology · 2019
    Review
  9. Moving the Cellular Peptidome by Transporters.Frontiers in cell and developmental biology · 2018
    Review
  10. Review
  11. Article
  12. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Valentina HerbringInstitute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt a.M., Germany.
Anja BäuckerInstitute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt a.M., Germany.
Simon TrowitzschInstitute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt a.M., Germany.
Robert TampéInstitute of Biochemistry, Biocenter, Goethe University Frankfurt, Max-von-Laue-Str. 9, 60438 Frankfurt a.M., Germany.
Goethe University Frankfurt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

As a centerpiece of antigen processing, the ATP-binding cassette transporter associated with antigen processing (TAP) became a main target for viral immune evasion. The herpesviral ICP47 inhibits TAP function, thereby suppressing an adaptive immune response. Here, we report on a thermostable ICP47-TAP complex, generated by fusion of different ICP47 fragments. These fusion complexes allowed us to determine the direction and positioning in the central cavity of TAP. ICP47-TAP fusion complexes are arrested in a stable conformation, as demonstrated by MHC I surface expression, melting temperature, and the mutual exclusion of herpesviral TAP inhibitors. We unveiled a conserved region next to the active domain of ICP47 as essential for the complete stabilization of the TAP complex. Binding of the active domain of ICP47 arrests TAP in an open inward facing conformation rendering the complex inaccessible for other viral factors. Based on our findings, we propose a dual interaction mechanism for ICP47. A per se destabilizing active domain inhibits the function of TAP, whereas a conserved C-terminal region additionally stabilizes the transporter. These new insights into the ICP47 inhibition mechanism can be applied for future structural analyses of the TAP complex.

Indexed as

Amino Acid SequenceAntigen PresentationATP Binding Cassette Transporter, Subfamily B, Member 2Cell LineHEK293 CellsHistocompatibility Antigens Class IHumansImmediate-Early ProteinsProtein ConformationProtein StabilityRecombinant Fusion ProteinsSequence AlignmentSimplexvirusTemperatureATP Binding Cassette Transporter, Subfamily B, Member 2Histocompatibility Antigens Class IICP47 protein, Herpes simplex virusImmediate-Early ProteinsRecombinant Fusion Proteins

Identifiers

PMID27845362
PMCPMC5109273
OpenAlexW2549379248

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.