Evidence map›Paper›PMID 32181350›Full record

ArticleScience advances2020

Probing biophysical sequence constraints within the transmembrane domains of rhodopsin by deep mutational scanning.

Wesley D Penn, Andrew G McKee, Charles P Kuntz, Hope Woods, Veronica Nash, Timothy C Gruenhagen, Francis J Roushar, Mahesh Chandak, Chris Hemmerich, Douglas B Rusch and 2 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
2.8field-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

32 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Deep mutational scan of the pore of the cold-sensing TRPM8 channel.bioRxiv : the preprint server for biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Novel Fosfomycin Resistance Mechanism inAntibiotics (Basel, Switzerland) · 2024
    Article
  13. Ribosomal frameshifting selectively modulates the assembly, function, and pharmacological rescue of a misfolded CFTR variant.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Molecular basis of proton-sensing by G protein-coupled receptors.bioRxiv : the preprint server for biology · 2024
    Article
  18. Article
  19. Review
  20. 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

12 authors at 2 institutions in 1 country.

Wesley D PennDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.ORCID 0000-0001-8930-4091
Andrew G McKeeDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.ORCID 0000-0003-1238-987X
Charles P KuntzDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.ORCID 0000-0002-9431-4961
Hope WoodsDepartment of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.ORCID 0000-0001-6615-545X
Veronica NashDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.ORCID 0000-0002-9400-4576
Timothy C GruenhagenDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Francis J RousharDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.
Mahesh ChandakDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.ORCID 0000-0001-5657-3877
Chris HemmerichCenter for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47405, USA.
Douglas B RuschCenter for Genomics and Bioinformatics, Indiana University, Bloomington, IN 47405, USA.ORCID 0000-0002-1066-2687
Jens MeilerDepartment of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.ORCID 0000-0001-8945-193X
Jonathan P SchlebachDepartment of Chemistry, Indiana University, Bloomington, IN 47405, USA.ORCID 0000-0003-0955-7633
Indiana University Bloomington · USVanderbilt University · US

Funding

MOLECULAR BIOPHYSICS TRAINING PROGRAM AT VANDERBILTT32GM008320 · NIGMS · VANDERBILT UNIVERSITY · PI CHAZIN, WALTER J. · 1989 to 2023
$7.9M
Topological Energetics and the Cellular Quality Control of Integral Membrane ProteinsR01GM129261 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI SCHLEBACH, JONATHAN PATRICK · 2018 to 2022
$1.5M
Graduate Program in Quantitative and Chemical Biology at Indiana University BloomT32GM109825 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI GIEDROC, DAVID P. · 2014 to 2018
$926k
NIGMS NIH HHS R01 GM129261NIGMS NIH HHS T32 GM008320NIGMS NIH HHS T32 GM109825
6 · The paper itself

Abstract

Membrane proteins must balance the sequence constraints associated with folding and function against the hydrophobicity required for solvation within the bilayer. We recently found the expression and maturation of rhodopsin are limited by the hydrophobicity of its seventh transmembrane domain (TM7), which contains polar residues that are essential for function. On the basis of these observations, we hypothesized that rhodopsin's expression should be less tolerant of mutations in TM7 relative to those within hydrophobic TM domains. To test this hypothesis, we used deep mutational scanning to compare the effects of 808 missense mutations on the plasma membrane expression of rhodopsin in HEK293T cells. Our results confirm that a higher proportion of mutations within TM7 (37%) decrease rhodopsin's plasma membrane expression relative to those within a hydrophobic TM domain (TM2, 25%). These results in conjunction with an evolutionary analysis suggest solvation energetics likely restricts the evolutionary sequence space of polar TM domains.

Indexed as

Cell MembraneGene ExpressionHEK293 CellsHumansHydrophobic and Hydrophilic InteractionsLipid BilayersModels, MolecularMutationProtein DomainsProtein FoldingProtein Structure, SecondaryRecombinant ProteinsRhodopsinSolubilityThermodynamicsLipid BilayersRecombinant ProteinsRhodopsin

Identifiers

PMID32181350
PMCPMC7056298
OpenAlexW3009209436

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.