Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/12677
Title: Asymmetric mode of Ca²⁺-S100A4 interaction with nonmuscle myosin IIA generates nanomolar affinity required for filament remodeling.
Authors: 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
First Published: 4-Apr-2012
Citation: STRUCTURE, 2012, 20 (4), pp. 654-666
Abstract: 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.
DOI Link: 10.1016/j.str.2012.02.002
eISSN: 1878-4186
Links: http://hdl.handle.net/2381/12677
Type: Journal Article
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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