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Structural insights into integrin α 5 β 1 opening by fibronectin ligand

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Schumacher, Stephanie, Dedden, Dirk, Nunez, Roberto Vazquez, Matoba, Kyoko, Takagi, Junichi, Biertümpfel, Christian, Mizuno, Naoko·2021·Science Advances
DOI 10.1126/sciadv.abe9716PMC PMC8104898
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Abstract

Integrin α 5 β 1 structures in resting and active states with ligand fibronectin reveal key interactions for integrin opening.

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  • A model of dimeric ANGPT2147-496 in complex with inactive, half-bent α5β1-integrin and TIE2 ECDs could be created without steric clashes while maintaining the overall geometry and interactions of the existing structures.

    “Interestingly, the model of the dimeric ANGPT2147–496 in complex with the inactive, half-bent α5β1-integrin and TIE2 ECDs could be created without steric clashes while maintaining the overall geometry and interactions of the existing structures found in this study and previously (13, 16, 54–56) (Figure 8, A and B, and Supplemental Video 2).”

    From Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling (2026) · cites this paper as [56]

  • ANGPT2147-496 adopts an elongated rod-like shape, with an estimated length of 15 nm.

    “Based on the SAXS data, ANGPT2147–496 adopts an elongated rod-like shape, with an estimated length of 15 nm, which is longer than the previously measured 9.5 nm distance between the upper legs of α5 and β1-integrins in the open active conformation of the α5β1-integrin heterodimer (56).”

    From Inactive β1-integrin acts as a junctional scaffold for angiopoietin/TIE2/FOXO1 signaling (2026) · cites this paper as [56]

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Authors
Schumacher, S., Dedden, D., Nunez, R. V., Matoba, K., Takagi, J., Biertümpfel, C., & Mizuno, N.
Affiliations
  • Max Planck Society (DE)
  • Laboratory of Structural Cell Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Dr., Bethesda, MD 20892, USA.
  • Institute for Protein Research, The University of Osaka (JP)
  • National Institutes of Health (US)
Corresponding author
  • Takagi, Junichi
  • Biertümpfel, Christian
  • Mizuno, Naoko
ORCID
Venue
Science Advances
Publisher
American Association for the Advancement of Science (AAAS)
Published
2021-05-07
Volume
7
Issue
19
ISSN
2375-2548 (ISSN-L)
DOI
10.1126/sciadv.abe9716
PMC
PMC8104898
OpenAlex
W3158808353
Cited by
150
References
1
Citations by year
2026: 27 · 2025: 31 · 2024: 37 · 2023: 36 · 2022: 17 · 2021: 2
FWCI
17.23
Type
journal article
Language
en
Open access
Licence
Locations
  • Science Advances (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
  • Boehringer Ingelheim (Plus3)
  • European Molecular Biology Organization (Young Investigator Program)
  • H2020 European Research Council (724209)
Topics
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords
alpha5beta1 integrin, fibronectin, integrin activation, ligand binding, integrin structure, extracellular matrix

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