Talin and kindlin use integrin tail allostery and direct binding to activate integrins
Open access
Date
2023-12Type
- Journal Article
ETH Bibliography
yes
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Abstract
Integrin affinity regulation, also termed integrin activation, is essential for metazoan life. Although talin and kindlin binding to the β-integrin cytoplasmic tail is indispensable for integrin activation, it is unknown how they achieve this function. By combining NMR, biochemistry and cell biology techniques, we found that talin and kindlin binding to the β-tail can induce a conformational change that increases talin affinity and decreases kindlin affinity toward it. We also discovered that this asymmetric affinity regulation is accompanied by a direct interaction between talin and kindlin, which promotes simultaneous binding of talin and kindlin to β-tails. Disrupting allosteric communication between the β-tail-binding sites of talin and kindlin or their direct interaction in cells severely compromised integrin functions. These data show how talin and kindlin cooperate to generate a small but critical population of ternary talin-β-integrin-kindlin complexes with high talin-integrin affinity and high dynamics. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000649084Publication status
publishedExternal links
Journal / series
Nature Structural & Molecular BiologyVolume
Pages / Article No.
Publisher
NatureOrganisational unit
03870 - Müller, Daniel J. / Müller, Daniel J.
Funding
182587 - Characterizing the cell cycle dependent regulation of adhesion to extracellular matrix proteins (SNF)
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ETH Bibliography
yes
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