Differential mechanical stability of filamin A rod segments

Hu Chen, Xiaoying Zhu, Peiwen Cong, Michael Sheetz, Fumihiko Nakamura, Jie Yan

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Prompted by recent reports suggesting that interaction of filamin A (FLNa) with its binding partners is regulated by mechanical force, we examined mechanical properties of FLNa domains using magnetic tweezers. FLNa, an actin cross-linking protein, consists of two subunits that dimerize through a C-terminal self-association domain. Each subunit contains an N-terminal spectrin-related actin-binding domain followed by 24 immunoglobulinlike (Ig) repeats. The Ig repeats in the rod 1 segment (repeats 1-15) are arranged as a linear array, whereas rod 2 (repeats 16-23) is more compact due to interdomain interactions. In the rod 1 segment, repeats 9-15 augment F-actin binding to a much greater extent than do repeats 1-8. Here, we report that the three segments are unfolded at different forces under the same loading rate. Remarkably, we found that repeats 16-23 are susceptible to forces of ∼10 pN or even less, whereas the repeats in the rod 1 segment can withstand significantly higher forces. The differential force response of FLNa Ig domains has broad implications, since these domains not only support the tension of actin network but also interact with many transmembrane and signaling proteins, mostly in the rod 2 segment. In particular, our finding of unfolding of repeats 16-23 at ∼10 pN or less is consistent with the hypothesized force-sensing function of the rod 2 segment in FLNa.

Original languageEnglish (US)
Pages (from-to)1231-1237
Number of pages7
JournalBiophysical Journal
Volume101
Issue number5
DOIs
StatePublished - Sep 7 2011
Externally publishedYes

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Filamins
Actins
Spectrin
Proteins

ASJC Scopus subject areas

  • Biophysics

Cite this

Differential mechanical stability of filamin A rod segments. / Chen, Hu; Zhu, Xiaoying; Cong, Peiwen; Sheetz, Michael; Nakamura, Fumihiko; Yan, Jie.

In: Biophysical Journal, Vol. 101, No. 5, 07.09.2011, p. 1231-1237.

Research output: Contribution to journalArticle

Chen, H, Zhu, X, Cong, P, Sheetz, M, Nakamura, F & Yan, J 2011, 'Differential mechanical stability of filamin A rod segments', Biophysical Journal, vol. 101, no. 5, pp. 1231-1237. https://doi.org/10.1016/j.bpj.2011.07.028
Chen, Hu ; Zhu, Xiaoying ; Cong, Peiwen ; Sheetz, Michael ; Nakamura, Fumihiko ; Yan, Jie. / Differential mechanical stability of filamin A rod segments. In: Biophysical Journal. 2011 ; Vol. 101, No. 5. pp. 1231-1237.
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