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Characterization of 14-3-3-? Interactions with integrin tails.

ABSTRACT: Integrins are a family of heterodimeric (?+?) 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 ?- and ?-integrin subunits. Talin is one well-known intracellular activator, but various other adaptors bind to integrin tails, including 14-3-3-?, ?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 ?2 integrin tail has been shown to modulate ?2/14-3-3-? interactions, and recently, the ?4 integrin tail was reported to bind to 14-3-3-? 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-? and the cytoplasmic tails of ?4, ?1, ?2 and ?3 integrins. The X-ray structure of the 14-3-3-?/?4 complex indicates a canonical binding mode for the ?4 phospho-peptide, but unexpected features are also observed: residues outside the consensus 14-3-3-? binding motif are shown to be essential for an efficient interaction; in contrast, a short ?2 phospho-peptide is sufficient for high-affinity binding to 14-3-3-?. In addition, we report novel 14-3-3-?/integrin tail interactions that are independent of phosphorylation. Of the integrin tails studied, the strongest interaction with 14-3-3-? is observed for the ?1A variant. In summary, new insights about 14-3-3-?/integrin tail interactions that have implications for the role of these molecular associations in cells are described.

SUBMITTER: Bonet R

PROVIDER: S-EPMC4068353 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Characterization of 14-3-3-ζ Interactions with integrin tails.

Bonet Roman R Vakonakis Ioannis I Campbell Iain D ID

Journal of molecular biology 20130611 17

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 d ...[more]

PMID: 23763993

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Dataset Information

Characterization of 14-3-3-? Interactions with integrin tails.

Publications

Characterization of 14-3-3-ζ Interactions with integrin tails.

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