Evidence map›Paper›PMID 40326394›Full record

ArticleFaraday discussions2025

Asymmetric membrane properties through a protein lens.

Joseph H Lorent, Angela Cabrera-Jojoa, Kandice R Levental, Ilya Levental, Edward Lyman

Abstract read
In one paragraph

Article in Faraday discussions, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. Sketching microprotein portraits.Protein science : a publication of the Protein Society · 2026
    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

5 authors.

Joseph H LorentCellular and Molecular Pharmacology (FACM), Louvain Drug Research Institute, UCLouvain, Avenue Mounier 73/1, B-1200 Brussels, Belgium. joseph.lorent@uclouvain.be.ORCID 0000-0002-7537-8521
Angela Cabrera-JojoaDepartment of Physics and Astronomy, University of Delaware, Newark, DE, USA.
Kandice R LeventalMolecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA, USA.ORCID 0000-0002-2234-3683
Ilya LeventalMolecular Physiology and Biophysics, University of Virginia School of Medicine, Charlottesville, VA, USA.ORCID 0000-0002-1206-9545
Edward LymanDepartment of Physics and Astronomy, University of Delaware, Newark, DE, USA.ORCID 0000-0003-4590-0363

Funding

Supplemental Postdoc: Lipid dependent GPCR signaling: Thermodynamics and mechanismsR35GM153273 · NIGMS · UNIVERSITY OF DELAWARE · PI Edward Ray Lyman · 2024 to 2026
$1.5M
NIGMS NIH HHS R35 GM153273
6 · The paper itself

Abstract

Plasma membranes are asymmetric, with each monolayer presenting specific lipid compositions and biophysical properties. Transmembrane domains (TMDs) of single-pass transmembrane proteins (spTMPs) have adapted their physico-chemical properties to these asymmetric constraints. In this study, we analysed the structural features of such TMDs across the tree of life to obtain information about their interaction with asymmetric membrane bilayers and predict species-specific membrane properties. We observed that TMDs in the plasma membranes of all eukaryotic species possess asymmetries in lipid accessible surface area (ASA), hydrophobicity, aromaticity and charge. Bacteria deviate from this trend, with strong differences between bacterial clades. Notably, TMDs in the Golgi and the endoplasmic reticulum of eukaryotic species display inverted profiles for accessible surface area, hydrophobicity and aromaticity compared to their plasma-membrane counterparts. To determine how well TMD profiles reflect average membrane properties, we performed molecular dynamics simulations of a spTMP in an asymmetric lipid bilayer whose composition approximates the human plasma membrane. The simulated spTMP was chosen to represent the average TMD properties of the human proteome. We compared the electron density profiles of the simulated asymmetric membrane to the average TMD profiles derived from the human proteome and observed that phospholipid acyl-chain density overlapped very well with TMD hydrophobicity, and phosphate group density with TMD charge. The profiles of phospholipid unsaturation in the acyl chains overlapped well with the average location of TMD phenylalanines in the cytoplasmic leaflet, while there was additional accumulation of large hydrophobic and aromatic residues in the membrane midplane, which had low acyl-chain density. This study reveals the complementarity of membrane and TMD properties in asymmetric membranes, suggesting that the properties of TMDs can be used to make predictions about the properties of their solvating membranes.

Indexed as

Cell MembraneLipid BilayersMembrane ProteinsHumansHydrophobic and Hydrophilic InteractionsMolecular Dynamics SimulationLipid BilayersMembrane Proteins

Identifiers

PMID40326394
PMCPMC12805673

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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.