Structural basis for RKIP binding with its substrate Raf1 kinase

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	Structural basis for RKIP binding with its substrate Raf1 kinase
	Wu, Zhihua ; Fu, Cuiping ; Shi, Lina ; Ruan, Lu ; Lin, Donghai ; Guo, Chenyun ; Lin DH(林东海) ; Guo CY(郭晨云)
刊名	http://dx.doi.org/10.1007/s10529-014-1558-6
	2014
关键词	Binding energy Diseases Fluorescence Nuclear magnetic resonance Nuclear magnetic resonance spectroscopy Proteins
英文摘要	Raf1 kinase inhibitor protein (RKIP) negatively regulates the Raf1/MEK/ERK pathway which is vital for cell growth and differentiation. It is also a biomarker in clinical cancer diagnosis. RKIP binds to the N-terminus of Raf1 kinase but little is known about the structural basis of RKIP binding with Raf1. Here, we demonstrate that the N-terminus of human Raf1 kinase (hRaf11-147aa) binds with human RKIP (hRKIP) at its ligand-binding pocket, loop "127-149", and the C-terminal helix by NMR experiments. D70, D72, E83, Y120, and Y181 were further verified as the key residues participating in the interaction of hRKIP and hRaf11-147aa. G143-R146 fragment was also critical for hRKIP binding with hRaf11-147aa, for its deletion decreased the binding affinity around 300 times, from 154 to 0.46 mM-1. Our results provide important structural clues for designing the lead compound that disrupts RKIP-Raf1 interaction. ? 2014 Springer Science+Business Media Dordrecht.
语种	英语
出版者	Kluwer Academic Publishers
内容类型	期刊论文
源URL	[http://dspace.xmu.edu.cn/handle/2288/89694]
专题	化学化工－已发表论文
推荐引用方式 GB/T 7714	Wu, Zhihua,Fu, Cuiping,Shi, Lina,et al. Structural basis for RKIP binding with its substrate Raf1 kinase[J]. http://dx.doi.org/10.1007/s10529-014-1558-6,2014.
APA	Wu, Zhihua.,Fu, Cuiping.,Shi, Lina.,Ruan, Lu.,Lin, Donghai.,...&郭晨云.(2014).Structural basis for RKIP binding with its substrate Raf1 kinase.http://dx.doi.org/10.1007/s10529-014-1558-6.
MLA	Wu, Zhihua,et al."Structural basis for RKIP binding with its substrate Raf1 kinase".http://dx.doi.org/10.1007/s10529-014-1558-6 (2014).