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  Structural insights into integrin alpha(5)beta(1) opening by fibronectin ligand

Schumacher, S., Dedden, D., Nunez, R. V., Matoba, K., Takagi, J., Biertuempfel, C., et al. (2021). Structural insights into integrin alpha(5)beta(1) opening by fibronectin ligand. Science Advances, 7(19): eabe9716. doi:10.1126/sciadv.abe9716.

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Open Access CC BY-NC

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 Creators:
Schumacher, Stephanie1, Author              
Dedden, Dirk1, Author              
Nunez, Roberto Vazquez2, Author
Matoba, Kyoko2, Author
Takagi, Junichi2, Author
Biertuempfel, Christian2, Author
Mizuno, Naoko1, Author              
Affiliations:
1Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565144              
2external, ou_persistent22              

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Free keywords: Science & Technology - Other Topics;
 Abstract: Integrin alpha(5)beta(1) is a major fibronectin receptor critical for cell migration. Upon complex formation, fibronectin and alpha(5)beta(1) undergo conformational changes. While this is key for cell-tissue connections, its mechanism is unknown. Here, we report cryo-electron microscopy structures of native human alpha(5)beta(1) with fibronectin to 3.1-angstrom resolution, and in its resting state to 4.6-angstrom resolution. The alpha(5)beta(1)-fibronectin complex revealed simultaneous interactions at the arginine-glycine-aspartate loop, the synergy site, and a newly identified binding site proximal to adjacent to metal ion-dependent adhesion site, inducing the translocation of helix alpha 1 to secure integrin opening. Resting alpha(5)beta(1) adopts an incompletely bent conformation, challenging the model of integrin sharp bending inhibiting ligand binding. Our biochemical and structural analyses showed that affinity of alpha(5) for fibronectin is increased with manganese ions (Mn2+) while adopting the half-bent conformation, indicating that ligand-binding affinity does not depend on conformation, and alpha(5)beta(1) opening is induced by ligand-binding.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published online
 Pages: 17
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: ISI: 000648332700020
DOI: 10.1126/sciadv.abe9716
 Degree: -

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Title: Science Advances
  Other : Sci. Adv.
Source Genre: Journal
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Publ. Info: Washington : AAAS
Pages: - Volume / Issue: 7 (19) Sequence Number: eabe9716 Start / End Page: - Identifier: ISSN: 2375-2548
CoNE: https://pure.mpg.de/cone/journals/resource/2375-2548