Evidence map›Paper›PMID 36889459›Full record

ArticleJournal of molecular biology2023

Activity and Structural Dynamics of Human ABCA1 in a Lipid Membrane.

Ashlee M Plummer-Medeiros, Alan T Culbertson, Claudio L Morales-Perez, Maofu Liao

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
7.0field-weighted citation impact, top 2% 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

16 citing papers in PubMed, 22 citations in OpenAlex.

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  5. A dual sensor regulates P-glycoprotein's structural plasticity.bioRxiv : the preprint server for biology · 2026
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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

4 authors at 2 institutions in 2 countries.

Ashlee M Plummer-MedeirosDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Bryn Mawr College Chemistry Department, 101 N Merion Avenue, Bryn Mawr, PA 19010, USA.
Alan T CulbertsonDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Roivant Sciences, Inc., 451 D Street, Boston, MA 02210, USA.
Claudio L Morales-PerezDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Generate Biomedicines, 4 Corporate Drive Andover, MA, 01810, USA.
Maofu LiaoDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Chemical Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: liaomf@sustech.edu.cn.
Harvard University · USBryn Mawr College · US

Funding

Structure of Sphingosine 1-phosphate ReceptorsF32GM136092 · NIGMS · HARVARD MEDICAL SCHOOL · PI CULBERTSON, ALAN THOMAS · 2020 to 2021
$131k
American Heart Association-American Stroke Association 18POST34030341NIGMS NIH HHS F32 GM136092
6 · The paper itself

Abstract

The human ATP-binding cassette (ABC) transporter ABCA1 plays a critical role in lipid homeostasis as it extracts sterols and phospholipids from the plasma membrane for excretion to the extracellular apolipoprotein A-I and subsequent formation of high-density lipoprotein (HDL) particles. Deleterious mutations of ABCA1 lead to sterol accumulation and are associated with atherosclerosis, poor cardiovascular outcomes, cancer, and Alzheimer's disease. The mechanism by which ABCA1 drives lipid movement is poorly understood, and a unified platform to produce active ABCA1 protein for both functional and structural studies has been missing. In this work, we established a stable expression system for both a human cell-based sterol export assay and protein purification for in vitro biochemical and structural studies. ABCA1 produced in this system was active in sterol export and displayed enhanced ATPase activity after reconstitution into a lipid bilayer. Our single-particle cryo-EM study of ABCA1 in nanodiscs showed protein induced membrane curvature, revealed multiple distinct conformations, and generated a structure of nanodisc-embedded ABCA1 at 4.0-Å resolution representing a previously unknown conformation. Comparison of different ABCA1 structures and molecular dynamics simulations demonstrates both concerted domain movements and conformational variations within each domain. Taken together, our platform for producing and characterizing ABCA1 in a lipid membrane enabled us to gain important mechanistic and structural insights and paves the way for investigating modulators that target the functions of ABCA1.

Indexed as

ATP Binding Cassette Transporter 1Cell MembraneMembrane LipidsSingle Molecule ImagingSterolsApolipoprotein A-IHumansLipid BilayersMutationPhospholipidsABCA1 protein, humanApolipoprotein A-IATP Binding Cassette Transporter 1Lipid BilayersMembrane LipidsPhospholipidsSterolsABC transportercholesterolcryo-electron microscopymembrane transportmembrane transporter reconstitution

Identifiers

PMID36889459
PMCPMC11540065
OpenAlexW4323304968

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.