Creating Conformational Entropy by Increasing Interdomain Mobility in Ligand Binding Regulation: A Revisit to N-Terminal Tandem PDZ Domains of PSD-95

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	Creating Conformational Entropy by Increasing Interdomain Mobility in Ligand Binding Regulation: A Revisit to N-Terminal Tandem PDZ Domains of PSD-95
	Wang, Wenning 1,2; Weng, Jingwei 1,2; Zhang, Xu 3; Liu, Maili 3; Zhang, Mingjie 4
刊名	JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
	2009-01-21
卷号	131 期号:2 页码:787-796
通讯作者	Wang, W (reprint author), Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China.
英文摘要	The two N-terminal PDZ domains of postsynaptic density protein-95 (PDS-95 PDZ1 and PDZ2) are closely connected in tandem by a conserved peptide linker of five amino acids. The interdomain orientation between PDZ1 and PDZ2 of the ligand-free PDZ12 tandem is restrained, and this conformational arrangement facilitates the synergistic binding of PDZ1 2 to multimeric targets.' The interdomain orientation of the target-bound state of PDZ12 is not known. Here, we have solved the structure of PDZ1 2 in complex with its binding domain from cypin. Both chemical shift data and residual dipolar coupling measurements showed that the restrained interdomain orientation disappeared upon cypin peptide binding. NMR-based relaxation experiments revealed slow interdomain motions in the PDZ12/cypin peptide complex. Molecular dynamics simulations also showed that the PDZ12/cypin complex has larger conformational flexibility than the ligand-free PDZ12. This dramatic change of protein dynamics provides extra conformational entropy upon ligand binding, thus enhancing the ligand binding affinity of the PDZ1 2 tandem. Modulation of ligand binding affinity through concerted interdomain structural and dynamic rearrangements may represent a general property of multidomain scaffold proteins.
WOS标题词	Science & Technology ; Physical Sciences
类目[WOS]	Chemistry, Multidisciplinary
研究领域[WOS]	Chemistry
关键词[WOS]	N-15 NMR RELAXATION ; MODEL-FREE APPROACH ; MOLECULAR-DYNAMICS ; BACKBONE DYNAMICS ; SCAFFOLD PROTEINS ; DIPOLAR COUPLINGS ; TARGET BINDING ; COMPLEX ; ORGANIZATION ; PROGRAM
收录类别	SCI
语种	英语
WOS记录号	WOS:000262521800071
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/2281]
专题	武汉物理与数学研究所_2011年以前论文发表（包括2011年）
作者单位	1.Fudan Univ, Dept Chem, Shanghai 200433, Peoples R China 2.Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China 3.Chinese Acad Sci, Wuhan Inst Phys & Math, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan 430071, Peoples R China 4.Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong, Peoples R China
推荐引用方式 GB/T 7714	Wang, Wenning,Weng, Jingwei,Zhang, Xu,et al. Creating Conformational Entropy by Increasing Interdomain Mobility in Ligand Binding Regulation: A Revisit to N-Terminal Tandem PDZ Domains of PSD-95[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,2009,131(2):787-796.
APA	Wang, Wenning,Weng, Jingwei,Zhang, Xu,Liu, Maili,&Zhang, Mingjie.(2009).Creating Conformational Entropy by Increasing Interdomain Mobility in Ligand Binding Regulation: A Revisit to N-Terminal Tandem PDZ Domains of PSD-95.JOURNAL OF THE AMERICAN CHEMICAL SOCIETY,131(2),787-796.
MLA	Wang, Wenning,et al."Creating Conformational Entropy by Increasing Interdomain Mobility in Ligand Binding Regulation: A Revisit to N-Terminal Tandem PDZ Domains of PSD-95".JOURNAL OF THE AMERICAN CHEMICAL SOCIETY 131.2(2009):787-796.