Year: 2021
Type: article
Abstract: Ras dimerization is critical for Raf activation. Here we show that the Ras binding domain of Raf (Raf-RBD) induces robust Ras dimerization at low surface densities on supported lipid bilayers and, to a lesser extent, in solution as observed by size exclusion chromatography and confirmed by SAXS. Community network analysis based on molecular dynamics simulations shows robust allosteric connections linking the two Raf-RBD D113 residues located in the Galectin scaffold protein binding site of each Raf-RBD molecule and 85 Å apart on opposite ends of the dimer complex. Our results suggest that Raf-RBD binding and Ras dimerization are concerted events that lead to a high-affinity signaling complex at the membrane that we propose is an essential unit in the macromolecular assembly of higher order Ras/Raf/Galectin complexes important for signaling through the Ras/Raf/MEK/ERK pathway.
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Awards: Structure and function of plexin - co-receptor interactions, Breakthrough Molecular Dynamics Research via an Anton2 Supercomputer, ECM geometrical and mechanical properties modulate RTK signaling, Configurational and internal dynamics of protein-protein complexes, G8122203363, Allosteric elements in the superfamily of small GTPases
OpenAlex ID: W3135289027