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Kinetic Advantage of Intrinsically Disordered Proteins in Coupled Folding-Binding Process: A Critical Assessment of the "Fly-Casting" Mechanism
Huang, Yongqi; Liu, Zhirong1
2009-11-13
Source PublicationJOURNAL OF MOLECULAR BIOLOGY
ISSN0022-2836
Volume393Issue:5Pages:1143-1159
AbstractIntrinsically disordered proteins (IDPs) are recognized to play important roles in many biological functions such as transcription and translation regulation, cellular signal transduction, protein phosphorylation, and molecular assemblies. The coupling of folding with binding through a "fly-casting" mechanism has been proposed to account for the fast binding kinetics of IDPs. In this article, experimental data from the literature were collated to verify the kinetic advantages of IDPs, while molecular simulations were performed to clarify the origin of the kinetic advantages. The phosphorylated KID-kinase-inducible domain interacting domain (KIX) complex was used as an example in the simulations. By modifying a coarse-grained model with a native-centric Go-like potential, we were able to continuously tune the degree of disorder of the phosphorylated KID domain and thus investigate the intrinsic role of chain flexibility in binding kinetics. The simulations show that the "fly-casting" effect is not only due to the greater capture radii of IDPs. The coupling of folding with binding of IDPs leads to a significant reduction in binding free-energy barrier. Such a reduction accelerates the binding process. Although the greater capture radius has been regarded as the main factor in promoting the binding rate of IDPs, we found that this parameter will also lead to the slower translational diffusion of IDPs when compared with ordered proteins. As a result, the capture rate of IDPs was found to be slower than that of ordered proteins. The main origin of the faster binding for IDPs are the fewer encounter times required before the formation of the final binding complex. The roles of the interchain native contacts fraction (Q(b)) and the mass-center distance (Delta R) as reaction coordinates are also discussed. (C) 2009 Elsevier Ltd. All rights reserved.
Keyword"fly-casting" Mechanism Intrinsically Disordered Protein Coupled Folding-binding Coarse-grained Simulation Capture Radius
DOI10.1016/j.jmb.2009.09.010
Indexed BySCI
Language英语
WOS IDWOS:000271596500013
PublisherACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Citation statistics
Cited Times:182[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.iccas.ac.cn/handle/121111/67270
Collection中国科学院化学研究所
Corresponding AuthorLiu, Zhirong
Affiliation1.Peking Univ, Coll Chem & Mol Engn, Ctr Theoret Biol, State Key Lab Struct Chem Unstable & Stable Speci, Beijing 100871, Peoples R China
2.Peking Univ, Beijing Natl Lab Mol Sci, Beijing 100871, Peoples R China
Recommended Citation
GB/T 7714
Huang, Yongqi,Liu, Zhirong. Kinetic Advantage of Intrinsically Disordered Proteins in Coupled Folding-Binding Process: A Critical Assessment of the "Fly-Casting" Mechanism[J]. JOURNAL OF MOLECULAR BIOLOGY,2009,393(5):1143-1159.
APA Huang, Yongqi,&Liu, Zhirong.(2009).Kinetic Advantage of Intrinsically Disordered Proteins in Coupled Folding-Binding Process: A Critical Assessment of the "Fly-Casting" Mechanism.JOURNAL OF MOLECULAR BIOLOGY,393(5),1143-1159.
MLA Huang, Yongqi,et al."Kinetic Advantage of Intrinsically Disordered Proteins in Coupled Folding-Binding Process: A Critical Assessment of the "Fly-Casting" Mechanism".JOURNAL OF MOLECULAR BIOLOGY 393.5(2009):1143-1159.
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