4G0N

Crystal Structure of wt H-Ras-GppNHp bound to the RBD of Raf Kinase

4G0N の概要

• エントリーDOI: 10.2210/pdb4g0n/pdb
• 分子名称: GTPase HRas, RAF proto-oncogene serine/threonine-protein kinase, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (8 entities in total)
• 機能のキーワード: h-ras, ras, raf kinase, raf, gtpase, allosteric regulation, intrinsic hydrolysis, protein-protein interaction, ras/raf/mek/erk, kinase, gtp binding, protein binding-transferase complex, protein binding/transferase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Cell membrane. Isoform 2: Nucleus: P01112; Cytoplasm: P04049
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 28605.54

構造登録者

Fetics, S.K.,Kearney, B.M.,Buhrman, G.,Mattos, C. (登録日: 2012-07-09, 公開日: 2013-07-17, 最終更新日: 2024-02-28)

主引用文献

Fetics, S.K.,Guterres, H.,Kearney, B.M.,Buhrman, G.,Ma, B.,Nussinov, R.,Mattos, C.
Allosteric Effects of the Oncogenic RasQ61L Mutant on Raf-RBD.
Structure, 23:505-516, 2015

PubMed Abstract: The Ras/Raf/MEK/ERK signal transduction pathway is a major regulator of cell proliferation activated by Ras-guanosine triphosphate (GTP). The oncogenic mutant RasQ61L is not able to hydrolyze GTP in the presence of Raf and thus is a constitutive activator of this mitogenic pathway. The Ras/Raf interaction is essential for the activation of the Raf kinase domain through a currently unknown mechanism. We present the crystal structures of the Ras-GppNHp/Raf-RBD and RasQ61L-GppNHp/Raf-RBD complexes, which, in combination with MD simulations, reveal differences in allosteric interactions leading from the Ras/Raf interface to the Ras calcium-binding site and to the remote Raf-RBD loop L4. In the presence of Raf, the RasQ61L mutant has a rigid switch II relative to the wild-type and increased flexibility at the interface with switch I, which propagates across Raf-RBD. We show that in addition to local perturbations on Ras, RasQ61L has substantial long-range effects on the Ras allosteric lobe and on Raf-RBD.

PubMed: 25684575
DOI: 10.1016/j.str.2014.12.017

実験手法

X-RAY DIFFRACTION (2.45 Å)