Ezrin interacts with S100A4 via both its N- and C-terminal domains

Beáta Biri-Kovács, Bence Kiss, Henrietta Vadászi, Gergo Gógl, Gyula Pálfy, György Török, L. Homolya, A. Bodor, L. Nyitray

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Ezrin belongs to the ERM (ezrin, radixin, moesin) protein family that has a role in cell morphology changes, adhesion and migration as an organizer of the cortical cytoskeleton by linking actin filaments to the apical membrane of epithelial cells. It is highly expressed in a variety of human cancers and promotes metastasis. Members of the Ca2+-binding EF-hand containing S100 proteins have similar pathological properties; they are overexpressed in cancer cells and involved in metastatic processes. In this study, using tryptophan fluorescence and stopped-flow kinetics, we show that S100A4 binds to the N-terminal ERM domain (N-ERMAD) of ezrin with a micromolar affinity. The binding involves the F2 lobe of the N-ERMAD and follows an induced fit kinetic mechanism. Interestingly, S100A4 binds also to the unstructured C-terminal actin binding domain (C-ERMAD) with similar affinity. Using NMR spectroscopy, we characterized the complex of S100A4 with the C-ERMAD and demonstrate that no ternary complex is simultaneously formed with the two ezrin domains. Furthermore, we show that S100A4 co-localizes with ezrin in HEK-293T cells. However, S100A4 very weakly binds to full-length ezrin in vitro indicating that the interaction of S100A4 with ezrin requires other regulatory events such as protein phosphorylation and/or membrane binding, shifting the conformational equilibrium of ezrin towards the open state. As both proteins play an important role in promoting metastasis, the characterization of their interaction could shed more light on the molecular events contributing to this pathological process.

Original languageEnglish
Article numbere0177489
JournalPLoS One
Volume12
Issue number5
DOIs
Publication statusPublished - May 1 2017

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metastasis
actin
kinetics
family relations
proteins
protein phosphorylation
cytoskeleton
microfilaments
tryptophan
adhesion
nuclear magnetic resonance spectroscopy
Actins
epithelial cells
hands
fluorescence
cells
calcium
neoplasms
Neoplasm Metastasis
EF Hand Motifs

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Biri-Kovács, B., Kiss, B., Vadászi, H., Gógl, G., Pálfy, G., Török, G., ... Nyitray, L. (2017). Ezrin interacts with S100A4 via both its N- and C-terminal domains. PLoS One, 12(5), [e0177489]. https://doi.org/10.1371/journal.pone.0177489

Ezrin interacts with S100A4 via both its N- and C-terminal domains. / Biri-Kovács, Beáta; Kiss, Bence; Vadászi, Henrietta; Gógl, Gergo; Pálfy, Gyula; Török, György; Homolya, L.; Bodor, A.; Nyitray, L.

In: PLoS One, Vol. 12, No. 5, e0177489, 01.05.2017.

Research output: Contribution to journalArticle

Biri-Kovács, B, Kiss, B, Vadászi, H, Gógl, G, Pálfy, G, Török, G, Homolya, L, Bodor, A & Nyitray, L 2017, 'Ezrin interacts with S100A4 via both its N- and C-terminal domains', PLoS One, vol. 12, no. 5, e0177489. https://doi.org/10.1371/journal.pone.0177489
Biri-Kovács B, Kiss B, Vadászi H, Gógl G, Pálfy G, Török G et al. Ezrin interacts with S100A4 via both its N- and C-terminal domains. PLoS One. 2017 May 1;12(5). e0177489. https://doi.org/10.1371/journal.pone.0177489
Biri-Kovács, Beáta ; Kiss, Bence ; Vadászi, Henrietta ; Gógl, Gergo ; Pálfy, Gyula ; Török, György ; Homolya, L. ; Bodor, A. ; Nyitray, L. / Ezrin interacts with S100A4 via both its N- and C-terminal domains. In: PLoS One. 2017 ; Vol. 12, No. 5.
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