Evidence map›Paper›PMID 32978801›Full record

ReviewFEBS letters2020

Picky ABCG5/G8 and promiscuous ABCG2 - a tale of fatty diets and drug toxicity.

Narakorn Khunweeraphong, James Mitchell-White, Dániel Szöllősi, Toka Hussein, Karl Kuchler, Ian D Kerr, Thomas Stockner, Jyh-Yeuan Lee

Open access · hybridAbstract readReview
In one paragraph

Review in FEBS letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.5field-weighted citation impact, top 15% 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

9 citing papers in PubMed, 31 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

8 authors at 4 institutions in 3 countries.

Narakorn KhunweeraphongMax Perutz Labs Vienna, Campus Vienna Biocenter, Center for Medical Biochemistry, Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-8457-2230
James Mitchell-WhiteSchool of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.ORCID 0000-0003-2818-8538
Dániel SzöllősiCenter for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0003-4641-3065
Toka HusseinDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.ORCID 0000-0002-7530-0126
Karl KuchlerMax Perutz Labs Vienna, Campus Vienna Biocenter, Center for Medical Biochemistry, Medical University of Vienna, Vienna, Austria.ORCID 0000-0003-2719-5955
Ian D KerrSchool of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, UK.ORCID 0000-0002-7544-8454
Thomas StocknerCenter for Physiology and Pharmacology, Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0002-7071-8283
Jyh-Yeuan LeeDepartment of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.ORCID 0000-0003-1799-2416
Max Perutz Labs · ATMedical University of Vienna · ATUniversity of Nottingham · GBUniversity of Ottawa · CA

Funding

Biotechnology and Biological Sciences Research Council BB/S001611/1
6 · The paper itself

Abstract

Structural data on ABCG5/G8 and ABCG2 reveal a unique molecular architecture for subfamily G ATP-binding cassette (ABCG) transporters and disclose putative substrate-binding sites. ABCG5/G8 and ABCG2 appear to use several unique structural motifs to execute transport, including the triple helical bundles, the membrane-embedded polar relay, the re-entry helices, and a hydrophobic valve. Interestingly, ABCG2 shows extreme substrate promiscuity, whereas ABCG5/G8 transports only sterol molecules. ABCG2 structures suggest a large internal cavity, serving as a binding region for substrates and inhibitors, while mutational and pharmacological analyses support the notion of multiple binding sites. By contrast, ABCG5/G8 shows a collapsed cavity of insufficient size to hold substrates. Indeed, mutational analyses indicate a sterol-binding site at the hydrophobic interface between the transporter and the lipid bilayer. In this review, we highlight key differences and similarities between ABCG2 and ABCG5/G8 structures. We further discuss the relevance of distinct and shared structural features in the context of their physiological functions. Finally, we elaborate on how ABCG2 and ABCG5/G8 could pave the way for studies on other ABCG transporters.

Indexed as

DietDrug-Related Side Effects and Adverse ReactionsAnimalsATP Binding Cassette Transporter, Subfamily G, Member 2ATP Binding Cassette Transporter, Subfamily G, Member 5ATP Binding Cassette Transporter, Subfamily G, Member 8Evolution, MolecularHumansModels, MolecularPharmaceutical PreparationsSubstrate SpecificityATP Binding Cassette Transporter, Subfamily G, Member 2ATP Binding Cassette Transporter, Subfamily G, Member 5ATP Binding Cassette Transporter, Subfamily G, Member 8Pharmaceutical PreparationsABCG2ABCG5ABCG8ATP-binding cassettecholesterol effluxmembranesmultidrug resistancepolar relaystructural biology

Identifiers

PMID32978801
PMCPMC7756502
OpenAlexW3088668630

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.