Evidence map›Paper›PMID 30850607›Full record

ArticleNature communications2019

Structural determinants of lipid specificity within Ups/PRELI lipid transfer proteins.

Xeni Miliara, Takashi Tatsuta, Jamie-Lee Berry, Sarah L Rouse, Kübra Solak, Dror S Chorev, Di Wu, Carol V Robinson, Stephen Matthews, Thomas Langer

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

40 citing papers in PubMed, 59 citations in OpenAlex.

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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

10 authors at 3 institutions in 2 countries.

Xeni MiliaraDepartment of Life Sciences, Imperial College London, Sir Ernst Chain Building, South Kensington, London, SW7 2AZ, UK.
Takashi TatsutaMax-Planck-Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931, Cologne, Germany.
Jamie-Lee BerryDepartment of Life Sciences, Imperial College London, Sir Ernst Chain Building, South Kensington, London, SW7 2AZ, UK.
Sarah L RouseDepartment of Life Sciences, Imperial College London, Sir Ernst Chain Building, South Kensington, London, SW7 2AZ, UK.
Kübra SolakMax-Planck-Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931, Cologne, Germany.
Dror S ChorevPhysical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3TA, UK.
Di WuPhysical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3TA, UK.
Carol V RobinsonPhysical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, South Parks Road, Oxford, OX1 3TA, UK.
Stephen MatthewsDepartment of Life Sciences, Imperial College London, Sir Ernst Chain Building, South Kensington, London, SW7 2AZ, UK. s.j.matthews@imperial.ac.uk.ORCID http://orcid.org/0000-0003-0676-0927
Thomas LangerMax-Planck-Institute for Biology of Ageing, Joseph-Stelzmann-Str. 9b, 50931, Cologne, Germany. Langer@age.mpg.de.ORCID http://orcid.org/0000-0003-1250-1462
Imperial College London · GBUniversity of Cologne · DEUniversity of Oxford · GB

Funding

Medical Research Council MC_PC_17162Medical Research Council MR/M019403/1Medical Research Council MR/P028225/1Medical Research Council MR/S021191/1
6 · The paper itself

Abstract

Conserved lipid transfer proteins of the Ups/PRELI family regulate lipid accumulation in mitochondria by shuttling phospholipids in a lipid-specific manner across the intermembrane space. Here, we combine structural analysis, unbiased genetic approaches in yeast and molecular dynamics simulations to unravel determinants of lipid specificity within the conserved Ups/PRELI family. We present structures of human PRELID1-TRIAP1 and PRELID3b-TRIAP1 complexes, which exert lipid transfer activity for phosphatidic acid and phosphatidylserine, respectively. Reverse yeast genetic screens identify critical amino acid exchanges that broaden and swap their lipid specificities. We find that amino acids involved in head group recognition and the hydrophobicity of flexible loops regulate lipid entry into the binding cavity. Molecular dynamics simulations reveal different membrane orientations of PRELID1 and PRELID3b during the stepwise release of lipids. Our experiments thus define the structural determinants of lipid specificity and the dynamics of lipid interactions by Ups/PRELI proteins.

Indexed as

Amino Acid SequenceBinding SitesBiological TransportCarrier ProteinsCloning, MolecularCrystallography, X-RayEscherichia coliGene ExpressionGenetic VectorsHumansIntracellular Signaling Peptides and ProteinsMitochondrial ProteinsModels, MolecularPhosphatidic AcidsPhosphatidylserinesProtein BindingCarrier ProteinsIntracellular Signaling Peptides and Proteinslipid transfer proteinMitochondrial ProteinsPhosphatidic AcidsPhosphatidylserinesPRELID1 protein, humanProtein IsoformsRecombinant ProteinsSaccharomyces cerevisiae ProteinsTRIAP1 protein, humanUps1 protein, S cerevisiae

Identifiers

PMID30850607
PMCPMC6408443
OpenAlexW2919876613

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

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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.