Evidence map›Paper›PMID 35660161›Full record

ArticleStructure (London, England : 1993)2022

Cholesterol occupies the lipid translocation pathway to block phospholipid scrambling by a G protein-coupled receptor.

Giulia Morra, Asghar M Razavi, Anant K Menon, George Khelashvili

Abstract read
In one paragraph

Article in Structure (London, England : 1993), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. 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

4 authors.

Giulia MorraDepartment of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Avenue, Room LC-501C, New York, NY 10065, USA; Istituto di Scienze e Tecnologie Chimiche SCITEC, CNR, Via Mario Bianco 9, 20131 Milano, Italy.
Asghar M RazaviRoivant Sciences, New York, NY 10036, USA.
Anant K MenonDepartment of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA.
George KhelashviliDepartment of Physiology and Biophysics, Weill Cornell Medicine, 1300 York Avenue, Room LC-501C, New York, NY 10065, USA; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY 10065, USA. Electronic address: gek2009@med.cornell.edu.

Funding

VISION RESEARCHP30EY005722 · NEI · DUKE UNIVERSITY · PI Vadim Y Arshavsky · 1985 to 2026
$19.3M
Rhodopsin dimerization: mechanistic basis and functional consequencesR01EY027969 · NEI · WEILL MEDICAL COLL OF CORNELL UNIV · PI ARSHAVSKY, VADIM Y, BURNS, MARIE E · 2017 to 2020
$2.2M
Molecular mechanism of phospholipid scrambling by rhodopsinR21EY028314 · NEI · WEILL MEDICAL COLL OF CORNELL UNIV · PI KHELASHVILI, GEORGE, MENON, ANANT K · 2017 to 2018
$466k
NEI NIH HHS P30 EY005722NEI NIH HHS R01 EY027969NEI NIH HHS R21 EY028314
6 · The paper itself

Abstract

Class A (rhodopsin-like) G protein-coupled receptors (GPCRs) are constitutive phospholipid scramblases as evinced after their reconstitution into liposomes. Yet phospholipid scrambling is not detectable in the resting plasma membrane of mammalian cells that is replete with GPCRs. We considered whether cholesterol, a prominent component of the plasma membrane, limits the ability of GPCRs to scramble lipids. Our previous Markov State Model (MSM) analysis of molecular dynamics simulations of membrane-embedded opsin indicated that phospholipid headgroups traverse a dynamically revealed hydrophilic groove between transmembrane helices (TM) 6 and 7 while their tails remain in the bilayer. Here, we present comparative MSM analyses of 150-μs simulations of opsin in cholesterol-free and cholesterol-rich membranes. Our analyses reveal that cholesterol inhibits phospholipid scrambling by occupying the TM6/7 interface and stabilizing the closed groove conformation while itself undergoing flip-flop. This mechanism may explain the inability of GPCRs to scramble lipids at the plasma membrane.

Indexed as

Phospholipid Transfer ProteinsReceptors, G-Protein-CoupledAnimalsBiological TransportCholesterolLipid BilayersMammalsOpsinsPhospholipidsCholesterolLipid BilayersOpsinsPhospholipidsPhospholipid Transfer ProteinsReceptors, G-Protein-CoupledcholesterolGPCRMarkov State Modelmolecular dynamics simulationsrhodopsinscramblase

Identifiers

PMID35660161
PMCPMC9356978

What OpenQuestion holds

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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.