Evidence map›Paper›PMID 28718450›Full record

ArticleThe Journal of biological chemistry2017

Dynamics and energetics of the mammalian phosphatidylinositol transfer protein phospholipid exchange cycle.

Aby Grabon, Adam Orłowski, Ashutosh Tripathi, Joni Vuorio, Matti Javanainen, Tomasz Róg, Max Lönnfors, Mark I McDermott, Garland Siebert, Pentti Somerharju and 2 more

Open access · hybridAbstract readComparative Study
In one paragraph

Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.6field-weighted citation impact, top 18% 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

30 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Phosphatidylinositol transfer protein α binds microcolins in its open conformation.Acta crystallographica. Section D, Structural biology · 2026
    Article
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  15. Review
  16. Courier service for phosphatidylinositol: PITPs deliver on demand.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2021
    Review
  17. Review
  18. Mechanisms of nonvesicular lipid transport.The Journal of cell biology · 2021
    Review
  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 5 institutions in 5 countries.

Aby GrabonFrom the Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, Texas 77843.
Adam Orłowskithe Laboratory of Physics, Tampere University of Technology, FI-33720 Tampere, Finland.
Ashutosh TripathiFrom the Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, Texas 77843.
Joni Vuoriothe Laboratory of Physics, Tampere University of Technology, FI-33720 Tampere, Finland.
Matti Javanainenthe Laboratory of Physics, Tampere University of Technology, FI-33720 Tampere, Finland.
Tomasz Rógthe Laboratory of Physics, Tampere University of Technology, FI-33720 Tampere, Finland.
Max LönnforsFrom the Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, Texas 77843.
Mark I McDermottFrom the Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, Texas 77843.
Garland SiebertFrom the Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, Texas 77843.
Pentti Somerharjuthe Department of Biochemistry and Developmental Biology, University of Helsinki, P. O. Box 63, FI-00014 Helsinki, Finland.
Ilpo Vattulainenthe Laboratory of Physics, Tampere University of Technology, FI-33720 Tampere, Finland, ilpo.vattulainen@tut.fi.
Vytas A BankaitisFrom the Department of Molecular and Cellular Medicine, Texas A&M Health Science Center, College Station, Texas 77843, vytas@tamhsc.edu.
Texas A&M Health Science Center · USUniversity of Helsinki · FITampere University · FIHelsinki Institute of Physics · FITexas A&M University · US

Funding

Resource for Biocomputing Visualization and InformaticsP41GM103311 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIN, THOMAS E · 2012 to 2017
$8.2M
Functional Anatomy of Mammalian Phosphatidylinositol Transfer ProteinsR01GM112591 · NIGMS · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI BANKAITIS, VYTAS A · 2015 to 2018
$1.7M
NIGMS NIH HHS P41 GM103311NIGMS NIH HHS R01 GM112591
6 · The paper itself

Abstract

Phosphatidylinositol-transfer proteins (PITPs) regulate phosphoinositide signaling in eukaryotic cells. The defining feature of PITPs is their ability to exchange phosphatidylinositol (PtdIns) molecules between membranes, and this property is central to PITP-mediated regulation of lipid signaling. However, the details of the PITP-mediated lipid exchange cycle remain entirely obscure. Here, all-atom molecular dynamics simulations of the mammalian StART-like PtdIns/phosphatidylcholine (PtdCho) transfer protein PITPα, both on membrane bilayers and in solvated systems, informed downstream biochemical analyses that tested key aspects of the hypotheses generated by the molecular dynamics simulations. These studies provided five key insights into the PITPα lipid exchange cycle: (i) interaction of PITPα with the membrane is spontaneous and mediated by four specific protein substructures; (ii) the ability of PITPα to initiate closure around the PtdCho ligand is accompanied by loss of flexibility of two helix/loop regions, as well as of the C-terminal helix; (iii) the energy barrier of phospholipid extraction from the membrane is lowered by a network of hydrogen bonds between the lipid molecule and PITPα; (iv) the trajectory of PtdIns or PtdCho into and through the lipid-binding pocket is chaperoned by sets of PITPα residues conserved throughout the StART-like PITP family; and (v) conformational transitions in the C-terminal helix have specific functional involvements in PtdIns transfer activity. Taken together, these findings provide the first mechanistic description of key aspects of the PITPα PtdIns/PtdCho exchange cycle and offer a rationale for the high conservation of particular sets of residues across evolutionarily distant members of the metazoan StART-like PITP family.

Indexed as

Models, MolecularAmino Acid SequenceAmino Acid SubstitutionAnimalsApoproteinsBiological TransportComputational BiologyConserved SequenceEnergy TransferHydrogen BondingLigandsLipid BilayersMolecular Dynamics SimulationMutation, MissensePhosphatidylcholinesPhosphatidylinositolsApoproteinsLigandsLipid BilayersPhosphatidylcholinesPhosphatidylinositolsPhospholipid Transfer ProteinsPitpna protein, ratRecombinant Proteinslipidlipid-protein interactionmolecular dynamicsphosphoinositidesignaling

Identifiers

PMID28718450
PMCPMC5582838
OpenAlexW2738310514

What OpenQuestion holds

Textmetadata
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.