Toggle Main Menu Toggle Search

Open Access padlockePrints

Asymmetric Mode of Ca2+-S100A4 Interaction with Nonmuscle Myosin IIA Generates Nanomolar Affinity Required for Filament Remodeling

Lookup NU author(s): Dr Martyna Pastok

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.


Publication metadata

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

Altmetrics provided by Altmetric


Actions

Find at Newcastle University icon    Link to this publication


Share