A comprehensive analysis of RAS-effector interactions reveals interaction hotspots and new binding partners

Abstract

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Structure-based prediction of Ras-effector binding affinities and design of ‘branchegetic’ interface mutations

“…The binding affinities were taken from the predicted binding affinities (see Estimation of binding affinities), with the exception of RASSF3 for which we are not confident in our structural predictions. An experimentally determined binding affinity for RASSF3 was substituted from 61 . Additional sets of binding affinities based on the branch pruning analysis were evaluated as well.…”

Analysis of KRAS–Ligand Interaction Modes and Flexibilities Reveals the Binding Characteristics

“…3 Mutations in RAS can impact the preferences of different protein effectors to interact, leading to changes in downstream signaling pathways. 4 For example, the G12D-mutated KRAS activates MEK/ERK and PI3K/AKT signaling pathways in the non-small-cell lung cancer (NSCLC) cell line. 5 Indeed, mutations in and overexpression of RAS are found in about 30% of all human cancers, including pancreatic cancer, NSCLC, and breast cancer.…”

“…With guanosine nucleotide exchange factors and GTPase-activating proteins, RAS plays a critical role in cell signaling pathways that regulate cell growth, proliferation, differentiation, and apoptosis . Mutations in RAS can impact the preferences of different protein effectors to interact, leading to changes in downstream signaling pathways . For example, the G12D-mutated KRAS activates MEK/ERK and PI3K/AKT signaling pathways in the non-small-cell lung cancer (NSCLC) cell line .…”

Systematic Analysis of KRAS-ligand Interaction Modes and Flexibilities Reveals the Binding Characteristics

“…With guanosine nucleotide exchange factors and GTPase-activating proteins, RAS plays a critical role in cell signaling pathways that regulate cell growth, proliferation, differentiation, and apoptosis 3 . Mutations in RAS can impact the preferences of different protein effectors to interact leading to changes in downstream signaling pathways 4 . For example, the G12D-mutated KRAS activates MEK/ERK and PI3K/AKT signaling pathways in the non-small-cell lung cancer (NSCLC) cell line 5 .…”