7JHP

Crystal structure of HRas in complex with the Ras-binding and cysteine-rich domains of CRaf-kinase

7JHP の概要

• エントリーDOI: 10.2210/pdb7jhp/pdb
• 分子名称: GTPase HRas, RAF proto-oncogene serine/threonine-protein kinase, PHOSPHOAMINOPHOSPHONIC ACID-GUANYLATE ESTER, ... (6 entities in total)
• 機能のキーワード: ras, raf, rbd, crd, signaling protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 34862.48

構造登録者

Cookis, T.,Mattos, C. (登録日: 2020-07-21, 公開日: 2020-08-05, 最終更新日: 2023-10-18)

主引用文献

Cookis, T.,Mattos, C.
Crystal Structure Reveals the Full Ras-Raf Interface and Advances Mechanistic Understanding of Raf Activation.
Biomolecules, 11:-, 2021

PubMed Abstract: Ras and Raf-kinase interact through the Ras-binding (RBD) and cysteine-rich domains (CRD) of Raf to signal through the mitogen-activated protein kinase pathway, yet the molecular mechanism leading to Raf activation has remained elusive. We present the 2.8 Å crystal structure of the HRas-CRaf-RBD_CRD complex showing the Ras-Raf interface as a continuous surface on Ras, as seen in the KRas-CRaf-RBD_CRD structure. In molecular dynamics simulations of a Ras dimer model formed through the α4-α5 interface, the CRD is dynamic and located between the two Ras protomers, poised for direct or allosteric modulation of functionally relevant regions of Ras and Raf. We propose a molecular model in which Ras binding is involved in the release of Raf autoinhibition while the Ras-Raf complex dimerizes to promote a platform for signal amplification, with Raf-CRD centrally located to impact regulation and function.

PubMed: 34356620
DOI: 10.3390/biom11070996

実験手法

X-RAY DIFFRACTION (2.766 Å)