2LNK

Solution structure of Ca-bound S100A4 in complex with non-muscle myosin IIA

Summary for 2LNK

• Entry DOI: 10.2210/pdb2lnk/pdb
• NMR Information: BMRB: 18169
• Descriptor: Myosin heavy chain, non-muscle IIa, Protein S100-A4 (2 entities in total)
• Functional Keywords: ef-hand, calcium binding, all alpha, metal binding protein, calcium binding protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 30811.26

Authors

Barsukov, I.L.,Elliott, P.R. (deposition date: 2011-12-30, release date: 2012-04-25, Last modification date: 2024-05-15)

Primary citation

Elliott, P.R.,Irvine, A.F.,Jung, H.S.,Tozawa, K.,Pastok, M.W.,Picone, R.,Badyal, S.K.,Basran, J.,Rudland, P.S.,Barraclough, R.,Lian, L.Y.,Bagshaw, C.R.,Kriajevska, M.,Barsukov, I.L.
Asymmetric Mode of Ca(2+)-S100A4 Interaction with Nonmuscle Myosin IIA Generates Nanomolar Affinity Required for Filament Remodeling.
Structure, 20:654-666, 2012

PubMed 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.

PubMed: 22483112
DOI: 10.1016/j.str.2012.02.002

Experimental method

SOLUTION NMR