Jung, Youn Hee Choi, Yoonjoo Seo, Hyo-Deok Seo, Moon-Hyeong Kim, Hak-Sung 2024-01-12T02:32:22Z 2024-01-12T02:32:22Z 2023-02-16 2023-02 0006-291X https://pubs.kist.re.kr/handle/201004/75809 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 conformationselective protein binders were shown to effectively block the interaction between active KRAS and RASbinding domain of BRAF, suppressing the KRAS-mediated downstream signaling. (c) 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC license (http://creativecommons.org/licenses/by-nc/4.0/). English Academic Press A conformation-selective protein binder for a KRAS mutant inhibits the interaction between RAS and RAF Article 10.1016/j.bbrc.2023.01.019 1 Biochemical and Biophysical Research Communications, v.645, pp.110 - 117 Biochemical and Biophysical Research Communications 645 110 117 Y scie scopus 000931513100001 Biochemistry & Molecular Biology Biophysics Biochemistry & Molecular Biology Biophysics Article KRAS Repebody Conformational selectivity