Evidence map›Paper›PMID 31969014›Full record

ArticleArteriosclerosis, thrombosis, and vascular biology2020

Cryo-Electron Microscopy Structure of the αIIbβ3-Abciximab Complex.

Dragana Nešić, Yixiao Zhang, Aleksandar Spasic, Jihong Li, Davide Provasi, Marta Filizola, Thomas Walz, Barry S Coller

Open access · bronzeAbstract read
In one paragraph

Article in Arteriosclerosis, thrombosis, and vascular biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
1.4field-weighted citation impact, top 16% 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

19 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
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  10. Peptide Antibodies: Current Status.Methods in molecular biology (Clifton, N.J.) · 2024
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  11. Review
  12. Family-wide analysis of integrin structures predicted by AlphaFold2.bioRxiv : the preprint server for biology · 2023
    Article
  13. Family-wide analysis of integrin structures predicted by AlphaFold2.Computational and structural biotechnology journal · 2023
    Article
  14. Article
  15. Structural analysis of receptors and actin polarity in platelet protrusions.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  16. Article
  17. Article
  18. Review
  19. Current Challenges and Opportunities in Designing Protein-Protein Interaction Targeted Drugs.Advances and applications in bioinformatics and chemistry : AABC · 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

8 authors at 1 institution in 1 country.

Dragana NešićFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology (D.N., J.L., B.S.C.), Rockefeller University, NY.
Yixiao ZhangLaboratory of Molecular Electron Microscopy (Y.Z., T.W.), Rockefeller University, NY.
Aleksandar SpasicDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, NY (A.S., D.P., M.F.).
Jihong LiFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology (D.N., J.L., B.S.C.), Rockefeller University, NY.
Davide ProvasiDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, NY (A.S., D.P., M.F.).
Marta FilizolaDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, NY (A.S., D.P., M.F.).
Thomas WalzLaboratory of Molecular Electron Microscopy (Y.Z., T.W.), Rockefeller University, NY.
Barry S CollerFrom the Allen and Frances Adler Laboratory of Blood and Vascular Biology (D.N., J.L., B.S.C.), Rockefeller University, NY.
Rockefeller University · US

Funding

Developing, Demonstrating, and Disseminating Innovative Programs to Achieve Translational SuccessUL1TR001866 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY, KRUEGER, JAMES G · 2016 to 2025
$40.6M
Platelet Integrin AlphaIIbBeta3 Structure, Activation, and Ligand Binding: Fibrinogen, Fibrin, D-dimer, and von Willebrand FactorR01HL019278 · NHLBI · STATE UNIVERSITY NEW YORK STONY BROOK · PI Claudia Lorena Buitrago, Barry Coller · 1985 to 2026
$17.6M
Big Omics Data Engine 2 SupercomputerS10OD026880 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2019 to 2019
$2.0M
Transforming Genomics with 5 PB Big Omics Data Engine Cray CS300-AC SupercomputerS10OD018522 · OD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI KOVATCH, PATRICIA · 2014 to 2014
$1.9M
NCATS NIH HHS UL1 TR001866NHLBI NIH HHS R01 HL019278NIH HHS S10 OD018522NIH HHS S10 OD026880
6 · The paper itself

Abstract

objectiveThe αIIbβ3 antagonist antiplatelet drug abciximab is the chimeric antigen-binding fragment comprising the variable regions of murine monoclonal antibody 7E3 and the constant domains of human IgG1 and light chain κ. Previous mutagenesis studies suggested that abciximab binds to the β3 C177-C184 specificity-determining loop (SDL) and Trp129 on the adjacent β1-α1 helix. These studies could not, however, assess whether 7E3 or abciximab prevents fibrinogen binding by steric interference, disruption of either the αIIbβ3-binding pocket for fibrinogen or the β3 SDL (which is not part of the binding pocket but affects fibrinogen binding), or some combination of these effects. To address this gap, we used cryo-electron microscopy to determine the structure of the αIIbβ3-abciximab complex at 2.8 Å resolution. Approach and Results: The interacting surface of abciximab is comprised of residues from all 3 complementarity-determining regions of both the light and heavy chains, with high representation of aromatic residues. Binding is primarily to the β3 SDL and neighboring residues, the β1-α1 helix, and β3 residues Ser211, Val212 and Met335. Unexpectedly, the structure also indicated several interactions with αIIb. As judged by the cryo-electron microscopy model, molecular-dynamics simulations, and mutagenesis, the binding of abciximab does not appear to rely on the interaction with the αIIb residues and does not result in disruption of the fibrinogen-binding pocket; it does, however, compress and reduce the flexibility of the SDL.

conclusionsWe deduce that abciximab prevents ligand binding by steric interference, with a potential contribution via displacement of the SDL and limitation of the flexibility of the SDL residues.

Indexed as

Cryoelectron MicroscopyPlatelet Aggregation InhibitorsAbciximabBinding, CompetitiveBinding SitesHEK293 CellsHumansIntegrin alpha2Integrin beta3LigandsMolecular Dynamics SimulationMutagenesis, Site-DirectedMutationProtein BindingProtein Interaction Domains and MotifsRecombinant ProteinsAbciximabIntegrin alpha2Integrin beta3ITGA2B protein, humanITGB3 protein, humanLigandsPlatelet Aggregation InhibitorsRecombinant Proteinsabciximabcryo-electron microscopyfibrinogenmolecular-dynamics simulationsmutagenesis

Identifiers

PMID31969014
PMCPMC7047619
OpenAlexW3001337259

What OpenQuestion 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 OpenQuestion graph.