Asymmetric mode of Ca²âº-S100A4 interaction with nonmuscle myosin IIA generates nanomolar affinity required for filament remodeling.
Structure
; 20(4): 654-66, 2012 Apr 04.
Article
em En
| MEDLINE
| ID: mdl-22483112
ABSTRACT
Filament assembly of nonmuscle myosin IIA (NMIIA) is selectively regulated by the small Ca²âº-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 Ca²âº-dependent binding sites of each subunit in the dimer. Synergy between these sites leads to a very tight association (K(D) â¼1 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citoesqueleto
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Proteínas S100
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Cálcio
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Miosina não Muscular Tipo IIA
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Células Epiteliais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article