气候变化领域集成服务门户(CCPortal): Raf promotes dimerization of the Ras G-domain with increased allosteric connections

CCPortal

DOI	10.1073/pnas.2015648118
	Raf promotes dimerization of the Ras G-domain with increased allosteric connections
	Packer M.R.; Parker J.A.; Chung J.K.; Li Z.; Lee Y.K.; Cookis T.; Guterres H.; Alvarez S.; Hossain M.A.; Donnelly D.P.; Agar J.N.; Makowski L.; Buck M.; Groves J.T.; Mattos C.
发表日期	2021
ISSN	00278424
卷号	118 期号:10
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Allosteric connections; Dimerization; Raf; Ras
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180390
作者单位	Department of Chemistry and Chemical Biology, Northeastern University, Boston, MA 02115, United States; Department of Chemistry, University of California, Berkeley, CA 94720, United States; Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH 44106, United States; Department of Materials Science and Engineering, University of California, Berkeley, CA 94720, United States; Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, United States; Department of Bioengineering, Northeastern University, Boston, MA 02115, United States
推荐引用方式 GB/T 7714	Packer M.R.,Parker J.A.,Chung J.K.,et al. Raf promotes dimerization of the Ras G-domain with increased allosteric connections[J],2021,118(10).
APA	Packer M.R..,Parker J.A..,Chung J.K..,Li Z..,Lee Y.K..,...&Mattos C..(2021).Raf promotes dimerization of the Ras G-domain with increased allosteric connections.Proceedings of the National Academy of Sciences of the United States of America,118(10).
MLA	Packer M.R.,et al."Raf promotes dimerization of the Ras G-domain with increased allosteric connections".Proceedings of the National Academy of Sciences of the United States of America 118.10(2021).