Evidence map›Paper›PMID 27432949›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Directed evolution of a sphingomyelin flippase reveals mechanism of substrate backbone discrimination by a P4-ATPase.

Bartholomew P Roland, Todd R Graham

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. P-Type ATPase Apt1 of the Fungal PathogenJournal of fungi (Basel, Switzerland) · 2021
    Article
  5. Article
  6. Article
  7. Conserved mechanism of phospholipid substrate recognition by the P4-ATPase Neo1 from Saccharomyces cerevisiae.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Decoding P4-ATPase substrate interactions.Critical reviews in biochemistry and molecular biology
    Review
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

2 authors.

Bartholomew P RolandDepartment of Biological Sciences, Vanderbilt University, Nashville, TN 37235.ORCID 0000-0002-9033-9942
Todd R GrahamDepartment of Biological Sciences, Vanderbilt University, Nashville, TN 37235 tr.graham@vanderbilt.edu.

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Jin Chen · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Program in NeurogenomicsT32MH065215 · NIMH · VANDERBILT UNIVERSITY · PI ROGER J COLBRAN · 2002 to 2026
$6.4M
P4-ATPase mechanism of phospholipid translocationR01GM107978 · NIGMS · VANDERBILT UNIVERSITY · PI GRAHAM, TODD R · 2013 to 2021
$2.5M
Molecular Characterization of the Phospholipid Flippase Substrate PathwayF32GM116310 · NIGMS · VANDERBILT UNIVERSITY · PI ROLAND, BARTHOLOMEW P · 2015 to 2016
$109k
NCI NIH HHS P30 CA068485NIDDK NIH HHS P30 DK058404NIGMS NIH HHS F32 GM116310NIGMS NIH HHS R01 GM107978NIMH NIH HHS T32 MH065215
6 · The paper itself

Abstract

Phospholipid flippases in the type IV P-type ATPase (P4-ATPases) family establish membrane asymmetry and play critical roles in vesicular transport, cell polarity, signal transduction, and neurologic development. All characterized P4-ATPases flip glycerophospholipids across the bilayer to the cytosolic leaflet of the membrane, but how these enzymes distinguish glycerophospholipids from sphingolipids is not known. We used a directed evolution approach to examine the molecular mechanisms through which P4-ATPases discriminate substrate backbone. A mutagenesis screen in the yeast Saccharomyces cerevisiae has identified several gain-of-function mutations in the P4-ATPase Dnf1 that facilitate the transport of a novel lipid substrate, sphingomyelin. We found that a highly conserved asparagine (N220) in the first transmembrane segment is a key enforcer of glycerophospholipid selection, and specific substitutions at this site allow transport of sphingomyelin.

Indexed as

Gain of Function MutationAdenosine TriphosphatasesAmino Acid SequenceAsparagineATP-Binding Cassette TransportersBiological TransportCell MembraneDirected Molecular EvolutionMutagenesisSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSequence Homology, Amino AcidSphingomyelinsSubstrate SpecificityAdenosine TriphosphatasesAsparagineATP-Binding Cassette TransportersDnf1 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsSphingomyelinsdirected evolutionmembrane asymmetryP4-ATPasesphingomyelin

Identifiers

PMID27432949
PMCPMC4978280

What OpenQuestion holds

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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.