Evidence map›Paper›PMID 29170462›Full record

ArticleNature communications2017

Structure of Rap1b bound to talin reveals a pathway for triggering integrin activation.

Liang Zhu, Jun Yang, Thomas Bromberger, Ashley Holly, Fan Lu, Huan Liu, Kevin Sun, Sarah Klapproth, Jamila Hirbawi, Tatiana V Byzova and 3 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing papers in PubMed
7.1field-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

68 citing papers in PubMed, 101 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Divergent Functions of Rap1A and Rap1B in Endothelial Biology and Disease.International journal of molecular sciences · 2025
    Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Spatial Mechano-Signaling Regulation of GTPases through Non-Degradative Ubiquitination.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  15. [Molecular dynamics simulation of force-regulated interaction between talin and Rap1b].Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi · 2023
    Article
  16. Article
  17. Integrin βNature communications · 2023
    Article
  18. Article
  19. Article
  20. Article

8 more citing papers are in PubMed but not listed here.

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

13 authors at 3 institutions in 2 countries.

Liang ZhuDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Jun YangDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Thomas BrombergerMax-Planck-Institute of Biochemistry, Department of Molecular Medicine, 82152, Martinsried, Germany.
Ashley HollyDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Fan LuDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Huan LiuDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Kevin SunDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Sarah KlapprothMax-Planck-Institute of Biochemistry, Department of Molecular Medicine, 82152, Martinsried, Germany.
Jamila HirbawiDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Tatiana V ByzovaDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Edward F PlowDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA.
Markus MoserMax-Planck-Institute of Biochemistry, Department of Molecular Medicine, 82152, Martinsried, Germany. moser@biochem.mpg.de.
Jun QinDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH, 44195, USA. qinj@ccf.org.
Cleveland Clinic · USMax Planck Institute of Biochemistry · DECase Western Reserve University · US

Funding

Structure Basis for Talin-mediated Integrin ActivationP01HL073311 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BYZOVA, TATIANA V · 2004 to 2019
$27.4M
STRUCTURES AND MECHANISMS OF ANK REPEAT BEARING PROTEINSR01HL058758 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI JUN QIN · 1999 to 2026
$9.0M
Regulation of Integrins in Neovasculature DevelopmentR01HL071625 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BYZOVA, TATIANA V · 2003 to 2021
$7.3M
Activation of the beta-3 integrins: Role of the KindlinsR01HL096062 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI PLOW, EDWARD FRANKLIN · 2009 to 2022
$5.6M
NMR Structural Elucidation of Integrin ActivationR01GM062823 · NIGMS · CLEVELAND CLINIC LERNER COM-CWRU · PI QIN, JUN · 2002 to 2018
$5.1M
NHLBI NIH HHS P01 HL073311NHLBI NIH HHS R01 HL058758NHLBI NIH HHS R01 HL071625NHLBI NIH HHS R01 HL096062NIGMS NIH HHS R01 GM062823
6 · The paper itself

Abstract

Activation of transmembrane receptor integrin by talin is essential for inducing cell adhesion. However, the pathway that recruits talin to the membrane, which critically controls talin's action, remains elusive. Membrane-anchored mammalian small GTPase Rap1 is known to bind talin-F0 domain but the binding was shown to be weak and thus hardly studied. Here we show structurally that talin-F0 binds to human Rap1b like canonical Rap1 effectors despite little sequence homology, and disruption of the binding strongly impairs integrin activation, cell adhesion, and cell spreading. Furthermore, while being weak in conventional binary binding conditions, the Rap1b/talin interaction becomes strong upon attachment of activated Rap1b to vesicular membranes that mimic the agonist-induced microenvironment. These data identify a crucial Rap1-mediated membrane-targeting mechanism for talin to activate integrin. They further broadly caution the analyses of weak protein-protein interactions that may be pivotal for function but neglected in the absence of specific cellular microenvironments.

Indexed as

Amino Acid SequenceAnimalsCell AdhesionCell LineCell MembraneGuanosine TriphosphateHumansIntegrinsMiceModels, MolecularNuclear Magnetic Resonance, BiomolecularProtein BindingProtein Interaction Domains and Motifsrap GTP-Binding ProteinsRecombinant ProteinsTalinGuanosine TriphosphateIntegrinsRAP1B protein, humanrap GTP-Binding ProteinsRecombinant ProteinsTalinTln1 protein, mouse

Identifiers

PMID29170462
PMCPMC5701058
OpenAlexW2770325190

What OpenQuestion holds

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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.