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Journal Article

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

MPS-Authors
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Bromberger,  Thomas
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

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Klapproth,  Sarah
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

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Moser,  Markus
Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society;

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s41467-017-01822-8.pdf
(Publisher version), 4MB

Supplementary Material (public)

41467_2017_1822_MOESM1_ESM.pdf
(Supplementary material), 5MB

41467_2017_1822_MOESM2_ESM.pdf
(Supplementary material), 2MB

Citation

Zhu, L., Yang, J., Bromberger, T., Holly, A., Lu, F., Liu, H., et al. (2017). Structure of Rap1b bound to talin reveals a pathway for triggering integrin activation. Nature Communications, 1744 (2017). doi:10.1038/s41467-017-01822-8.


Cite as: https://hdl.handle.net/21.11116/0000-0001-6DFB-B
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.