C-terminal recognition by 14-3-3 proteins for surfase expression of membrane receptors

Brian Coblitz, Sojin Shikano, Meng Wu, Sandra B. Gabelli, Lisa M. Cockrell, Matt Spieker, Yoshiro Hanyu, Haian Fu, L. Mario Amzel, Min Li

Research output: Contribution to journalArticle

Abstract

Diverse functions of 14-3-3 proteins are directly coupled to their ability to interact with targeted peptide substrates. RSX(pS/pT)XP and RXΦX(pS/pT)XP are two canonical consensus binding motifs for 14-3-3 proteins representing the two common binding modes, modes I and II, between 14-3-3 and internal peptides. Using a genetic selection, we have screened a random peptide library and identified a group of C-terminal motifs, termed SWTY, capable of overriding an endoplasmic reticulum localization signal and redirecting membrane proteins to cell surface. Here we report that the C-terminal SWTY motif, although different from mode I and II consensus, binds tightly to 14-3-3 proteins with a dissociation constant (KD) of 0.17 μM, comparable with that of internal canonical binding peptides. We show that all residues but proline in -SWTX-COOH are compatible for the interaction and surface expression. Because SWTY-like sequences have been found in native proteins, these results support a broad significance of 14-3-3 interaction with protein C termini. The C-terminal binding consensus, mode III, represents an expansion of the repertoire of 14-3-3-targeted sequences.

Original languageEnglish (US)
Pages (from-to)36263-36272
Number of pages10
JournalJournal of Biological Chemistry
Volume280
Issue number43
DOIs
StatePublished - Oct 28 2005

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Coblitz, B., Shikano, S., Wu, M., Gabelli, S. B., Cockrell, L. M., Spieker, M., Hanyu, Y., Fu, H., Amzel, L. M., & Li, M. (2005). C-terminal recognition by 14-3-3 proteins for surfase expression of membrane receptors. Journal of Biological Chemistry, 280(43), 36263-36272. https://doi.org/10.1074/jbc.M507559200