Creating Conformational Entropy by Increasing Interdomain Mobility in Ligand Binding Regulation: A Revisit to N-Terminal Tandem PDZ Domains of PSD-95 | |
Wang, Wenning1,2; Weng, Jingwei1,2; Zhang, Xu3; Liu, Maili3; Zhang, Mingjie4 | |
刊名 | JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
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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. |
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