Characterization of 14-3-3-ζ interactions with integrin tails
Integrins are a family of heterodimeric (α+β) adhesion receptors that play key roles in many cellular processes. Integrins are unusual in that their functions can be modulated from both outside and inside the cell. Inside-out signaling is mediated by binding adaptor proteins to the flexible cytoplas...
| Main Authors: | , , |
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| Format: | Journal article |
| Language: | English |
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2013
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| _version_ | 1826264224713670656 |
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| author | Bonet, R Vakonakis, I Campbell, I |
| author_facet | Bonet, R Vakonakis, I Campbell, I |
| author_sort | Bonet, R |
| collection | OXFORD |
| description | Integrins are a family of heterodimeric (α+β) adhesion receptors that play key roles in many cellular processes. Integrins are unusual in that their functions can be modulated from both outside and inside the cell. Inside-out signaling is mediated by binding adaptor proteins to the flexible cytoplasmic tails of the α- and β-integrin subunits. Talin is one well-known intracellular activator, but various other adaptors bind to integrin tails, including 14-3-3-ζ, a member of the 14-3-3 family of dimeric proteins that have a preference for binding phosphorylated sequence motifs. Phosphorylation of a threonine in the β2 integrin tail has been shown to modulate β2/14-3-3-ζ interactions, and recently, the α4 integrin tail was reported to bind to 14-3-3-ζ and associate with paxillin in a ternary complex that is regulated by serine phosphorylation. Here, we use a range of biophysical techniques to characterize interactions between 14-3-3-ζ and the cytoplasmic tails of α4, β1, β2 and β3 integrins. The X-ray structure of the 14-3-3-ζ/α4 complex indicates a canonical binding mode for the α4 phospho-peptide, but unexpected features are also observed: residues outside the consensus 14-3-3-ζ binding motif are shown to be essential for an efficient interaction; in contrast, a short β2 phospho-peptide is sufficient for high-affinity binding to 14-3-3-ζ. In addition, we report novel 14-3-3-ζ/integrin tail interactions that are independent of phosphorylation. Of the integrin tails studied, the strongest interaction with 14-3-3-ζ is observed for the β1A variant. In summary, new insights about 14-3-3-ζ/integrin tail interactions that have implications for the role of these molecular associations in cells are described. © 2013 The Authors. |
| first_indexed | 2024-03-06T20:04:21Z |
| format | Journal article |
| id | oxford-uuid:286c0b4c-60f1-4fac-865d-88eb7bf35995 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T20:04:21Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:286c0b4c-60f1-4fac-865d-88eb7bf359952022-03-26T12:12:46ZCharacterization of 14-3-3-ζ interactions with integrin tailsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:286c0b4c-60f1-4fac-865d-88eb7bf35995EnglishSymplectic Elements at Oxford2013Bonet, RVakonakis, ICampbell, IIntegrins are a family of heterodimeric (α+β) adhesion receptors that play key roles in many cellular processes. Integrins are unusual in that their functions can be modulated from both outside and inside the cell. Inside-out signaling is mediated by binding adaptor proteins to the flexible cytoplasmic tails of the α- and β-integrin subunits. Talin is one well-known intracellular activator, but various other adaptors bind to integrin tails, including 14-3-3-ζ, a member of the 14-3-3 family of dimeric proteins that have a preference for binding phosphorylated sequence motifs. Phosphorylation of a threonine in the β2 integrin tail has been shown to modulate β2/14-3-3-ζ interactions, and recently, the α4 integrin tail was reported to bind to 14-3-3-ζ and associate with paxillin in a ternary complex that is regulated by serine phosphorylation. Here, we use a range of biophysical techniques to characterize interactions between 14-3-3-ζ and the cytoplasmic tails of α4, β1, β2 and β3 integrins. The X-ray structure of the 14-3-3-ζ/α4 complex indicates a canonical binding mode for the α4 phospho-peptide, but unexpected features are also observed: residues outside the consensus 14-3-3-ζ binding motif are shown to be essential for an efficient interaction; in contrast, a short β2 phospho-peptide is sufficient for high-affinity binding to 14-3-3-ζ. In addition, we report novel 14-3-3-ζ/integrin tail interactions that are independent of phosphorylation. Of the integrin tails studied, the strongest interaction with 14-3-3-ζ is observed for the β1A variant. In summary, new insights about 14-3-3-ζ/integrin tail interactions that have implications for the role of these molecular associations in cells are described. © 2013 The Authors. |
| spellingShingle | Bonet, R Vakonakis, I Campbell, I Characterization of 14-3-3-ζ interactions with integrin tails |
| title | Characterization of 14-3-3-ζ interactions with integrin tails |
| title_full | Characterization of 14-3-3-ζ interactions with integrin tails |
| title_fullStr | Characterization of 14-3-3-ζ interactions with integrin tails |
| title_full_unstemmed | Characterization of 14-3-3-ζ interactions with integrin tails |
| title_short | Characterization of 14-3-3-ζ interactions with integrin tails |
| title_sort | characterization of 14 3 3 ζ interactions with integrin tails |
| work_keys_str_mv | AT bonetr characterizationof1433zinteractionswithintegrintails AT vakonakisi characterizationof1433zinteractionswithintegrintails AT campbelli characterizationof1433zinteractionswithintegrintails |