Evidence map›Paper›PMID 32690595›Full record

ArticleJournal of lipid research2020

The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase.

John G Luz, Anne P Beigneux, DeeAnn K Asamoto, Cuiwen He, Wenxin Song, Christopher M Allan, Jazmin Morales, Yiping Tu, Adam Kwok, Thomas Cottle and 6 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of lipid research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.9field-weighted citation impact, top 12% 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

10 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3/8 activity.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  5. Article
  6. Article
  7. Inverse effects of APOC2 and ANGPTL4 on the conformational dynamics of lid-anchoring structures in lipoprotein lipase.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  8. A protein of capillary endothelial cells, GPIHBP1, is crucial for plasma triglyceride metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  9. Review
  10. Chylomicronemia from GPIHBP1 autoantibodies.Journal of lipid research · 2020
    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

16 authors at 5 institutions in 2 countries.

John G LuzDivision of Experimental Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Anne P BeigneuxDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
DeeAnn K AsamotoDepartment of Chemistry and Biochemistry, University of California San Diego, San Diego, CA, USA.
Cuiwen HeDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Wenxin SongDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Christopher M AllanDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Jazmin MoralesDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Yiping TuDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Adam KwokDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Thomas CottleDivision of Experimental Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Muthuraman MeiyappanAnalytical Development, Pharmaceutical Sciences, Takeda Pharmaceutical Company, Lexington, MA, USA.
Loren G FongDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Judy E KimDepartment of Chemistry and Biochemistry, University of California San Diego, San Diego, CA, USA.
Michael PlougFinsen Laboratory, Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0003-2215-4265
Stephen G YoungDepartment of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA sgyoung@mednet.ucla.edu gbirrane@bidmc.harvard.edu.
Gabriel BirraneDivision of Experimental Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA sgyoung@mednet.ucla.edu gbirrane@bidmc.harvard.edu.ORCID 0000-0002-1759-5499
University of California, Los Angeles · USBeth Israel Deaconess Medical Center · USUniversity of California San Diego · USTakeda (United States) · USUniversity of Copenhagen · DK

Funding

The Lipin Protein Family and Triglyceride Metabolism P01HL090553 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2008 to 2018
$23.3M
Understanding the Influence of Lipid Homeostasis on T cell FunctionP01HL146358 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2019 to 2023
$11.7M
Refining Physiologic Mechanisms for Intravascular Triglyceride MetabolismR01HL087228 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEIGNEUX, ANNE, FONG, LOREN GI · 2007 to 2024
$7.8M
Investigating Mechanisms for Lipid Transport in Health and DiseaseR35HL139725 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2018 to 2024
$6.1M
Defining mechanisms for lipid transport across capillary endothelial cellsR01HL125335 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI YOUNG, STEPHEN G. · 2015 to 2017
$1.2M
NHLBI NIH HHS P01 HL090553NHLBI NIH HHS P01 HL146358NHLBI NIH HHS R01 HL087228NHLBI NIH HHS R01 HL125335NHLBI NIH HHS R35 HL139725
6 · The paper itself

Abstract

For three decades, the LPL-specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short α-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the α-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL.

Indexed as

Antibodies, MonoclonalLipoprotein LipaseTryptophanAnimalsCrystallography, X-RayHumansMiceModels, MolecularProtein BindingAntibodies, MonoclonalLipoprotein LipaseTryptophanantibodieslipid metabolismprotein structuretriglyceridesX-ray crystallography

Identifiers

PMID32690595
PMCPMC7529051
OpenAlexW3044795862

What OpenQuestion holds

Textmetadata
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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.