ArticleStructure (London, England : 1993)2009
Differences in flexibility underlie functional differences in the Ras activators son of sevenless and Ras guanine nucleotide releasing factor 1.
Article in Structure (London, England : 1993), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Biophysical Characterization of RAS-SOS Complexes by Native Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2024Article
- 2'-Deoxy Guanosine Nucleotides Alter the Biochemical Properties of Ras.Biochemistry · 2023Article
- Molecular assemblies of the catalytic domain of SOS with KRas and oncogenic mutants.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Characterisation of HRas local signal transduction networks using engineered site-specific exchange factors.Small GTPases · 2020Article
- The Interdependent Activation of Son-of-Sevenless and Ras.Cold Spring Harbor perspectives in medicine · 2019Review
- Allosteric KRas4B Can Modulate SOS1 Fast and Slow Ras Activation Cycles.Biophysical journal · 2018Article
- Phosphorylation of SOS1 on tyrosine 1196 promotes its RAC GEF activity and contributes to BCR-ABL leukemogenesis.Leukemia · 2018Article
- A computationally engineered RAS rheostat reveals RAS-ERK signaling dynamics.Nature chemical biology · 2017Article
- Mechanistic and Evolutionary Insights from Comparative Enzymology of Phosphomonoesterases and Phosphodiesterases across the Alkaline Phosphatase Superfamily.Journal of the American Chemical Society · 2016Article
- Article
- Increased cell growth due to a new lipase-GEF (Phospholipase D2) fastly acting on Ras.Cellular signalling · 2013Article
- NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling.Nature structural & molecular biology · 2011Article
- STIM1, PKC-δ and RasGRP set a threshold for proapoptotic Erk signaling during B cell development.Nature immunology · 2011Article
- Regulation of Neuronal Function by Ras-GRF Exchange Factors.Genes & cancer · 2011Article
- Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
Corrections and comments
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Authors and funding
6 authors.
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Abstract
The Ras-specific nucleotide exchange factor Son of sevenless (Sos) is inactive without Ras bound to a distal allosteric site. In contrast, the catalytic domain of Ras guanine nucleotide releasing factor 1 (RasGRF1) is active intrinsically. By substituting residues from RasGRF1 into Sos, we have generated mutants of Sos with basal activity, partially relieved of their dependence on allosteric activation. We have performed molecular dynamics simulations showing how Ras binding to the allosteric site leads to a bias toward the active conformation of Sos. The trajectories show that Sos fluctuates between active and inactive conformations in the absence of Ras and that the activating mutations favor conformations of Sos that are more permissive to Ras binding at the catalytic site. In contrast, unliganded RasGRF1 fluctuates primarily among active conformations. Our results support the premise that the catalytic domain of Sos has evolved an allosteric activation mechanism that extends beyond the simple process of membrane recruitment.
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