Browse by author
Lookup NU author(s): Dr Martyna PastokORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Filament assembly of nonmuscle myosin IIA (NMIIA) is selectively regulated by the small Ca²⁺-binding protein, S100A4, which causes enhanced cell migration and metastasis in certain cancers. Our NMR structure shows that an S100A4 dimer binds to a single myosin heavy chain in an asymmetrical configuration. NMIIA in the complex forms a continuous helix that stretches across the surface of S100A4 and engages the Ca²⁺-dependent binding sites of each subunit in the dimer. Synergy between these sites leads to a very tight association (K(D) ∼1 nM) that is unique in the S100 family. Single-residue mutations that remove this synergy weaken binding and ameliorate the effects of S100A4 on NMIIA filament assembly and cell spreading in A431 human epithelial carcinoma cells. We propose a model for NMIIA filament disassembly by S100A4 in which initial binding to the unstructured NMIIA tail initiates unzipping of the coiled coil and disruption of filament packing.
Author(s): Elliott PR, Irvine AF, Jung HS, Tozawa K, Pastok MW, Picone R, Badyal SK, Basran J, Rudland PS, Barraclough R, Lian LY, Bagshaw CR, Kriajevska M, Barsukov IL
Publication type: Article
Publication status: Published
Journal: Structure
Year: 2012
Volume: 20
Issue: 4
Pages: 654-666
Print publication date: 04/04/2012
ISSN (print): 0969-2126
ISSN (electronic): 1878-4186
Publisher: Cell Press
URL: http://dx.doi.org/10.1016/j.str.2012.02.002
DOI: 10.1016/j.str.2012.02.002
PubMed id: PMC3343272
Altmetrics provided by Altmetric