Evidence map›Paper›PMID 38514628›Full record

ArticleNature communications2024

Mutational scanning pinpoints distinct binding sites of key ATGL regulators in lipolysis.

Johanna M Kohlmayr, Gernot F Grabner, Anna Nusser, Anna Höll, Verina Manojlović, Bettina Halwachs, Sarah Masser, Evelyne Jany-Luig, Hanna Engelke, Robert Zimmermann and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

7 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Coixol and Sinigrin fromPharmaceuticals (Basel, Switzerland) · 2025
    Article
  5. Article
  6. Essential Biology of Lipid Droplets.Annual review of biochemistry · 2025
    Review
  7. 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

11 authors at 1 institution in 1 country.

Johanna M KohlmayrInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria.
Gernot F GrabnerInstitute of Molecular Biosciences, Biochemistry, University of Graz, Graz, Austria.ORCID http://orcid.org/0000-0002-7110-9957
Anna NusserInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria.
Anna HöllInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria.ORCID http://orcid.org/0009-0000-8102-6138
Verina ManojlovićInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria.
Bettina HalwachsInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria.ORCID http://orcid.org/0000-0002-7082-9346
Sarah MasserInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria.ORCID http://orcid.org/0000-0002-5195-0650
Evelyne Jany-LuigInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria.ORCID http://orcid.org/0000-0003-0500-1689
Hanna EngelkeInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria.ORCID http://orcid.org/0000-0001-9529-9436
Robert ZimmermannInstitute of Molecular Biosciences, Biochemistry, University of Graz, Graz, Austria.
Ulrich StelzlInstitute of Pharmaceutical Sciences, Pharmaceutical Chemistry, University of Graz, Graz, Austria. ulrich.stelzl@uni-graz.at.ORCID http://orcid.org/0000-0003-2500-3585
University of Graz · AT

Funding

Austrian Science Fund FWF DOC 50Austrian Science Fund FWF P 30162
6 · The paper itself

Abstract

ATGL is a key enzyme in intracellular lipolysis and plays an important role in metabolic and cardiovascular diseases. ATGL is tightly regulated by a known set of protein-protein interaction partners with activating or inhibiting functions in the control of lipolysis. Here, we use deep mutational protein interaction perturbation scanning and generate comprehensive profiles of single amino acid variants that affect the interactions of ATGL with its regulatory partners: CGI-58, G0S2, PLIN1, PLIN5 and CIDEC. Twenty-three ATGL amino acid variants yield a specific interaction perturbation pattern when validated in co-immunoprecipitation experiments in mammalian cells. We identify and characterize eleven highly selective ATGL switch mutations which affect the interaction of one of the five partners without affecting the others. Switch mutations thus provide distinct interaction determinants for ATGL's key regulatory proteins at an amino acid resolution. When we test triglyceride hydrolase activity in vitro and lipolysis in cells, the activity patterns of the ATGL switch variants trace to their protein interaction profile. In the context of structural data, the integration of variant binding and activity profiles provides insights into the regulation of lipolysis and the impact of mutations in human disease.

Indexed as

LipaseLipolysisAmino AcidsAnimalsBinding SitesCell Cycle ProteinsHumansMammalsMutationAmino AcidsCell Cycle ProteinsLipase

Identifiers

PMID38514628
PMCPMC10958042
OpenAlexW4393055133

What Socratic 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 Socratic graph.