A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS

In this study, we designed a single-molecule assay to resolve the time between initial receptor-mediated membrane recruitment and the initiation of GEF activity of individual SOS molecules on microarrays of Ras-functionalized supported membranes. The rise-and-fall shape of the measured SOS activation time distribution and the long mean time scale to activation (~50 seconds) establish a basis for kinetic proofreading in the receptor-mediated activation of Ras. We further demonstrate that this kinetic proofreading is modulated by the LAT (linker for activation of T cells)–Grb2–SOS phosphotyrosine-driven phase transition at the membrane.

Source: ScienceNOW - March 6, 2019 Category: Science Authors: Huang, W. Y. C., Alvarez, S., Kondo, Y., Lee, Y. K., Chung, J. K., Lam, H. Y. M., Biswas, K. H., Kuriyan, J., Groves, J. T. Tags: Biochemistry, Cell Biology reports Source Type: news