Evidence map›Paper›PMID 30914719›Full record

ArticleScientific reports2019

Highly Mutable Linker Regions Regulate HIV-1 Rev Function and Stability.

Bhargavi Jayaraman, Jason D Fernandes, Shumin Yang, Cynthia Smith, Alan D Frankel

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.0field-weighted citation impact, top 24% 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

18 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Tuning Rex rules HTLV-1 pathogenesis.Frontiers in immunology · 2022
    Review
  14. Review
  15. HIV Rev-isited.Open biology · 2020
    Review
  16. Article
  17. Article
  18. 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

5 authors at 1 institution in 2 countries.

Bhargavi JayaramanDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, 94158, USA.
Jason D FernandesDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, 94158, USA.
Shumin YangDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, 94158, USA.
Cynthia SmithDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, 94158, USA.
Alan D FrankelDepartment of Biochemistry and Biophysics, University of California San Francisco, San Francisco, CA, 94158, USA. frankel@cgl.ucsf.edu.
University of California, San Francisco · US

Funding

X-ray Screening and Rapid Structure DeterminationP50GM082250 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KROGAN, NEVAN J · 2007 to 2018
$48.8M
PHARMACEUTICAL SCIENCES AND PHARMACOGENOMICST32GM007175 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AHITUV, NADAV, KROETZ, DEANNA L · 1985 to 2021
$7.1M
NIGMS NIH HHS P50 GM082250NIGMS NIH HHS T32 GM007175
6 · The paper itself

Abstract

HIV-1 Rev is an essential viral regulatory protein that facilitates the nuclear export of intron-containing viral mRNAs. It is organized into structured, functionally well-characterized motifs joined by less understood linker regions. Our recent competitive deep mutational scanning study confirmed many known constraints in Rev's established motifs, but also identified positions of mutational plasticity, most notably in surrounding linker regions. Here, we probe the mutational limits of these linkers by testing the activities of multiple truncation and mass substitution mutations. We find that these regions possess previously unknown structural, functional or regulatory roles, not apparent from systematic point mutational approaches. Specifically, the N- and C-termini of Rev contribute to protein stability; mutations in a turn that connects the two main helices of Rev have different effects in different contexts; and a linker region which connects the second helix of Rev to its nuclear export sequence has structural requirements for function. Thus, Rev function extends beyond its characterized motifs, and is tuned by determinants within seemingly plastic portions of its sequence. Additionally, Rev's ability to tolerate many of these massive truncations and substitutions illustrates the overall mutational and functional robustness inherent in this viral protein.

Indexed as

Amino Acid MotifsHEK293 CellsHIV-1HumansMutationProtein DomainsProtein Stabilityrev Gene Products, Human Immunodeficiency VirusStructure-Activity Relationshiprev Gene Products, Human Immunodeficiency Virusrev protein, Human Immunodeficiency Virus-1

Identifiers

PMID30914719
PMCPMC6435700
OpenAlexW2951109098

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.