3EG5

Crystal structure of MDIA1-TSH GBD-FH3 in complex with CDC42-GMPPNP

3EG5 の概要

• エントリーDOI: 10.2210/pdb3eg5/pdb
• 関連するPDBエントリー: 1Z2C 2BAP
• 分子名称: Cell division control protein 42 homolog, Protein diaphanous homolog 1, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (5 entities in total)
• 機能のキーワード: protein-protein complex, rho proteins, diaphanous, formins, armadillo repeat, g-protein, gtpase, alternative splicing, cell membrane, gtp-binding, lipoprotein, membrane, methylation, nucleotide-binding, prenylation, actin-binding, cell projection, coiled coil, cytoplasm, cytoskeleton, phosphoprotein, ubl conjugation, signaling protein
• 由来する生物種: Mus musculus (mouse); 詳細
• 細胞内の位置: Cell membrane; Lipid-anchor; Cytoplasmic side (Potential): P60766; Cell membrane: O08808
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 129099.80

構造登録者

Lammers, M.,Meyer, S.,Kuehlmann, D.,Wittinghofer, A. (登録日: 2008-09-10, 公開日: 2008-10-14, 最終更新日: 2023-11-01)

主引用文献

Lammers, M.,Meyer, S.,Kuhlmann, D.,Wittinghofer, A.
Specificity of Interactions between mDia Isoforms and Rho Proteins
J.Biol.Chem., 283:35236-35246, 2008

PubMed Abstract: Formins are key regulators of actin nucleation and polymerization. They contain formin homology 1 (FH1) and 2 (FH2) domains as the catalytic machinery for the formation of linear actin cables. A subclass of formins constitutes the Diaphanous-related formins, members of which are regulated by the binding of a small GTP-binding protein of the Rho subfamily. Binding of these molecular switch proteins to the regulatory N-terminal mDia(N), including the GTPase-binding domain, leads to the release of auto-inhibition. From the three mDia isoforms, mDia1 is activated only by Rho (RhoA, -B, and -C), in contrast to mDia2 and -3, which is also activated by Rac and Cdc42. Little is known about the determinants of specificity. Here we report on the interactions of RhoA, Rac1, and Cdc42 with mDia1 and an mDia1 mutant (mDia(N)-Thr-Ser-His (TSH)), which based on structural information should mimic mDia2 and -3. Specificity is analyzed by biochemical studies and a structural analysis of a complex between Cdc42.Gpp(NH)p and mDia(N)-TSH. A triple NNN motif in mDia1 (amino acids 164-166), corresponding to the TSH motif in mDia2/3 (amino acids 183-185 and 190-192), and the epitope interacting with the Rho insert helix are essential for high affinity binding. The triple N motif of mDia1 allows tight interaction with Rho because of the presence of Phe-106, whereas the corresponding His-104 in Rac and Cdc42 forms a complementary interface with the TSH motif in mDia2/3. We also show that the F106H and H104F mutations drastically alter the affinities and thermodynamics of mDia interactions.

PubMed: 18829452
DOI: 10.1074/jbc.M805634200

実験手法

X-RAY DIFFRACTION (2.7 Å)