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Updated: Aug 13, 2025

Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
A conformation-selective protein binder for a KRAS mutant inhibits the interaction between RAS and RAF
Youn Hee Jung1, Yoonjoo Choi2, Hyo-Deok Seo3
1Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung, 25451, South Korea.
Abstract:
Small GTPases are key signaling nodes that regulate the cellular processes and subcellular events, and their abnormal activities and dysregulations are closely linked with diverse cancers. Here, we report the development of conformation-selective protein binders for a KRAS mutant. The conformation-specific protein binders were selected from a repebody scaffold composed of LRR (Leucine-rich repeat) modules through phage display and modular engineering against constitute active conformation of KRAS. Epitope of the selected binders was mapped to be located close to switch I of KRAS. The conformation-selective protein binders were shown to effectively block the interaction between active KRAS and RAS-binding domain of BRAF, suppressing the KRAS-mediated downstream signaling.
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