3TPQ

Crystal structure of wild-type MAL RPEL domain in complex with five G-actins

3TPQ の概要

• エントリーDOI: 10.2210/pdb3tpq/pdb
• 関連するPDBエントリー: 3TPM 3TPO
• 分子名称: Actin, alpha skeletal muscle, MAL, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: regulation of nuclear import, contractile protein-transcription complex, contractile protein/transcription
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cytoplasm, cytoskeleton: P68135
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 225803.40

構造登録者

Hirano, H.,Matsuura, Y. (登録日: 2011-09-08, 公開日: 2011-10-12, 最終更新日: 2023-11-01)

主引用文献

Hirano, H.,Matsuura, Y.
Sensing actin dynamics: structural basis for G-actin-sensitive nuclear import of MAL
Biochem.Biophys.Res.Commun., 414:373-378, 2011

PubMed Abstract: The coordination of cytoskeletal actin dynamics with gene expression reprogramming is emerging as a crucial mechanism to control diverse cellular processes, including cell migration, differentiation and neuronal circuit assembly. The actin-binding transcriptional coactivator MAL (also known as MRTF-A/MKL1/BSAC) senses G-actin concentration and transduces Rho GTPase signals to serum response factor (SRF). MAL rapidly shuttles between the cytoplasm and the nucleus in unstimulated cells but Rho-induced depletion of G-actin leads to MAL nuclear accumulation and activation of transcription of SRF:MAL-target genes. Although the molecular and structural basis of actin-regulated nucleocytoplasmic shuttling of MAL is not understood fully, it is proposed that nuclear import of MAL is mediated by importin α/β heterodimer, and that G-actin competes with importin α/β for the binding to MAL. Here we present structural, biochemical and cell biological evidence that MAL has a classical bipartite nuclear localization signal (NLS) in the N-terminal 'RPEL' domain containing Arg-Pro-X-X-X-Glu-Leu (RPEL) motifs. The NLS residues of MAL adopt an extended conformation and bind along the surface groove of importin-α, interacting with the major- and minor-NLS binding sites. We also present a crystal structure of wild-type MAL RPEL domain in complex with five G-actins. Comparison of the importin-α- and actin-complexes revealed that the binding of G-actins to MAL is associated with folding of NLS residues into a helical conformation that is inappropriate for importin-α recognition.

PubMed: 21964294
DOI: 10.1016/j.bbrc.2011.09.079

実験手法

X-RAY DIFFRACTION (3.45 Å)