Ras–Raf protein–protein interface (null)

The Ras–Raf protein–protein interface refers to a critical molecular contact surface between activated, membrane-bound Ras (a small GTPase) and the Ras-binding (RBD) and cysteine-rich (CRD) domains of Raf kinases (ARaf, BRaf, CRaf), which initiates the Ras–Raf–MEK–ERK signaling cascade fundamentally responsible for transducing growth and survival signals from cell surface receptors to the nucleus[1][4][7]. Formation of this interface brings Raf to the plasma membrane, drives a conformational change releasing Raf from autoinhibition (often stabilized by 14-3-3 proteins), and enables Raf dimerization and subsequent kinase activation[1][4][5]. This signaling axis is essential for normal cellular proliferation but is commonly hijacked in cancer via mutations in Ras or Raf proteins, leading to constitutive pathway activation and tumorigenesis[1][3][5]. Pharmacologically, the Ras–Raf interface was long considered "undruggable" due to its dynamic, relatively flat surface, but recent efforts have yielded small molecules that can disrupt this interface and thereby inhibit downstream signaling[2][6]. Targeting this interaction remains a high-priority area in oncology drug development, especially for tumors driven by oncogenic KRAS or BRAF mutations[6].

Other names

Ras–Raf interaction interfaceRas–Raf binding interfaceRas–Raf complexRas/Raf protein–protein interaction

Inhibition of Ras–Raf interaction (blocks signal transmission from Ras to Raf, preventing downstream pathway activation such as MEK/ERK signaling); Disruption of protein–protein complex formation (direct interface inhibition)