Piconewton-Scale Analysis of Ras-BRaf Signal Transduction with   Single-Molecule Force Spectroscopy

doi:10.1002/smll.201701972

CORC > 北京大学 > 生命科学学院

	Piconewton-Scale Analysis of Ras-BRaf Signal Transduction with Single-Molecule Force Spectroscopy
	Lim, Chae-Seok ; Wen, Cheng ; Sheng, Yanghui ; Wang, Guangfu ; Zhou, Zhuan ; Wang, Shiqiang ; Zhang, Huaye ; Ye, Anpei ; Zhu, J. Julius
刊名	SMALL
	2017
关键词	AMPA RECEPTOR TRAFFICKING CYSTEINE-RICH DOMAIN SYNAPTIC PLASTICITY OPTICAL TWEEZERS ACTIVATION MECHANISMS INSERTION KINASES DISPLAY BINDING
DOI	10.1002/smll.201701972
英文摘要	Intermolecular interactions dominate the behavior of signal transduction in various physiological and pathological cell processes, yet assessing these interactions remains a challenging task. Here, this study reports a single-molecule force spectroscopic method that enables functional delineation of two interaction sites (approximate to 35 pN and approximate to 90 pN) between signaling effectors Ras and BRaf in the canonical mitogen-activated protein kinase (MAPK) pathway. This analysis reveals mutations on BRaf at Q257 and A246, two sites frequently linked to cardio-faciocutaneous syndrome, result in approximate to 10-30 pN alterations in Ras. BRaf intermolecular binding force. The magnitude of changes in Ras. BRaf binding force correlates with the size of alterations in protein affinity and in alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-sensitive glutamate receptor(-R)-mediated synaptic transmission in neurons expressing replacement BRaf mutants, and predicts the extent of learning impairments in animals expressing replacement BRaf mutants. These results establish single-molecule force spectroscopy as an effective platform for evaluating the piconewton-level interaction of signaling molecules and predicting the behavior outcome of signal transduction.; National Research Foundation of Korea [NRF-2016R1D1A1B03931525]; National Natural Science Foundation of China, Beijing [NSFC30728012, NSFC31330024, NSFCU1636110, NSFC5102019]; Chinese Ministry of Education Project 111 Program [B13026]; National Key R&D Program of China [2016YFA0500400, 2016YFA0500401]; NIH [NS065183, NS089578, NS053570, NS091452, NS094980, NS092548]; SCI(E); ARTICLE; 40; 13
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/484596]
专题	生命科学学院信息科学技术学院
推荐引用方式 GB/T 7714	Lim, Chae-Seok,Wen, Cheng,Sheng, Yanghui,et al. Piconewton-Scale Analysis of Ras-BRaf Signal Transduction with Single-Molecule Force Spectroscopy[J]. SMALL,2017.
APA	Lim, Chae-Seok.,Wen, Cheng.,Sheng, Yanghui.,Wang, Guangfu.,Zhou, Zhuan.,...&Zhu, J. Julius.(2017).Piconewton-Scale Analysis of Ras-BRaf Signal Transduction with Single-Molecule Force Spectroscopy.SMALL.
MLA	Lim, Chae-Seok,et al."Piconewton-Scale Analysis of Ras-BRaf Signal Transduction with Single-Molecule Force Spectroscopy".SMALL (2017).