title: Mechanical perturbation of filamin A immunoglobulin repeats 20-21 reveals potential non-equilibrium mechanochemical partner binding function.
abstract: The actin crosslinking protein filamin A (FLNa) mediates mechanotransduction, a conversion of mechanical forces into cellular biochemical signals to regulate cell growth and survival. To provide more quantitative insight into this process, we report results using magnetic tweezers that relate mechanical force to conformational changes of FLNa immunoglobulin-like repeats (IgFLNa) 20-21, previously identified as a mechanosensing domain. We determined the force magnitudes required to unfold previously identified structural organizations of the β-strands in the two domains: IgFLNa 20 unfolds at ~15 pN and IgFLNa 21 unfolding requires significantly larger forces. Unfolded domain IgFLNa 20 can exist in two different conformational states, which lead to different refolding kinetics of the IgFLNa 20 and imply a significant impact on the reformation of the domain pair at reduced force values. We discuss the relevance of the findings to force bearing and mechanosensing functions of FLNa.
authors.affiliation: Mechanobiology Institute, National University of Singapore, Singapore 117411.
authors.forename: Hu
authors.initials: H
authors.lastname: Chen
authors.forename: Saranya
authors.initials: S
authors.lastname: Chandrasekar
authors.forename: Michael P
authors.initials: MP
authors.lastname: Sheetz
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Stossel
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nakamura
authors.forename: Jie
authors.initials: J
authors.lastname: Yan
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism; D064448:Filamins / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D058849:Protein Refolding; D058767:Protein Unfolding
chemical_list: D000199:Actins; D064448:Filamins; D010455:Peptides