3ZWH

Ca2+-bound S100A4 C3S, C81S, C86S and F45W mutant complexed with myosin IIA

3ZWH の概要

• エントリーDOI: 10.2210/pdb3zwh/pdb
• 関連するPDBエントリー: 1M31
• 分子名称: PROTEIN S100-A4, MYOSIN-9, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: ca-binding protein-motor protein complex, s100 proteins, ef-hand, ca-binding protein/motor protein
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton (By similarity): P35579
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 29757.96

構造登録者

Kiss, B.,Duelli, A.,Radnai, L.,Kekesi, A.K.,Katona, G.,Nyitray, L. (登録日: 2011-07-31, 公開日: 2012-04-04, 最終更新日: 2023-12-20)

主引用文献

Kiss, B.,Duelli, A.,Radnai, L.,Kekesi, K.A.,Katona, G.,Nyitray, L.
Crystal Structure of the S100A4-Nonmuscle Myosin Iia Tail Fragment Complex Reveals an Asymmetric Target Binding Mechanism.
Proc.Natl.Acad.Sci.USA, 109:6048-, 2012

PubMed Abstract: S100A4 is a member of the S100 family of calcium-binding proteins that is directly involved in tumor metastasis. It binds to the nonmuscle myosin IIA (NMIIA) tail near the assembly competence domain (ACD) promoting filament disassembly, which could be associated with increasing metastatic potential of tumor cells. Here, we investigate the mechanism of S100A4-NMIIA interaction based on binding studies and the crystal structure of S100A4 in complex with a 45-residue-long myosin heavy chain fragment. Interestingly, we also find that S100A4 binds as strongly to a homologous heavy chain fragment of nonmuscle myosin IIC as to NMIIA. The structure of the S100A4-NMIIA complex reveals a unique mode of interaction in the S100 family: A single, predominantly α-helical myosin chain is wrapped around the Ca(2+)-bound S100A4 dimer occupying both hydrophobic binding pockets. Thermal denaturation experiments of coiled-coil forming NMIIA fragments indicate that the coiled-coil partially unwinds upon S100A4 binding. Based on these results, we propose a model for NMIIA filament disassembly: Part of the random coil tailpiece and the C-terminal residues of the coiled-coil are wrapped around an S100A4 dimer disrupting the ACD and resulting in filament dissociation. The description of the complex will facilitate the design of specific drugs that interfere with the S100A4-NMIIA interaction.

PubMed: 22460785
DOI: 10.1073/PNAS.1114732109

実験手法

X-RAY DIFFRACTION (1.94 Å)