title: Differential mechanical stability of filamin A rod segments.
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.
authors: Mechanobiology Institute, National University of Singapore, Singapore.
authors: Hu
authors: H
authors: Chen
authors: Xiaoying
authors: X
authors: Zhu
authors: Peiwen
authors: P
authors: Cong
authors: Michael P
authors: MP
authors: Sheetz
authors: Fumihiko
authors: F
authors: Nakamura
authors: Jie
authors: J
authors: Yan
mesh_terms: D001696:Biomechanical Phenomena; D003285:Contractile Proteins / Q000737:chemistry* / Q000378:metabolism; D064448:Filamins; D007136:Immunoglobulins / Q000737:chemistry; D055595:Mechanical Phenomena; D008840:Microfilament Proteins / Q000737:chemistry* / Q000378:metabolism; D055550:Protein Stability; D017434:Protein Structure, Tertiary
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D007136:Immunoglobulins; D008840:Microfilament Proteins