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学科主题基础医学
Contributions of Conserved TPLH Tetrapeptides to the Conformational Stability of Ankyrin Repeat Proteins
Guo, Yi2; Yuan, Chunhua3; Tian, Feng4; Huang, Kun5; Weghorst, Christopher M.1,6; Tsai, Ming-Daw7,8,9; Li, Junan1,6
关键词ankyrin repeat TPLH motif gankyrin P16 stability
刊名JOURNAL OF MOLECULAR BIOLOGY
2010-05-28
DOI10.1016/j.jmb.2010.04.010
399期:1页:168-181
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
资助者National Institutes of Health ; National Institutes of Health
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]TUMOR-SUPPRESSOR P16(INK4A) ; KAPPA-B-ALPHA ; COMBINATORIAL LIBRARIES ; GANKYRIN ; INK4 ; P53 ; PREFERENCES ; ONCOPROTEIN ; INHIBITION ; P18(INK4C)
英文摘要

Ankyrin repeat (AR) proteins are one of the most abundant classes of repeat proteins and are involved in numerous physiological processes. These proteins are composed of various numbers of AR motifs stacked in a nearly linear fashion to adopt an elongated and nonglobular architecture. One salient feature prevalent in such a structural unit is the TPLH tetrapeptide or a close variant, T/SxxH, which initiates the helix-turn-helix conformation and presumably contributes to conformational stability through a hydrogen-bonding network. In the present study, we investigated the roles of T/SxxH motif in the stability, structure, and function of AR proteins by a systematic and rationalized mutagenic study on, followed by biochemical and biophysical characterization of, gankyrin, an oncogenic protein composed of seven ARs and six T/SxxH tetrapeptides, and P16, a tumor suppressor with four ARs but no TPLH tetrapeptide. Our results showed that this tetrapeptide is ineffectual on global structure and function, but contributes significantly to conformational stability when its stabilizing potentials are fully realized in the local conformation, including (1) the intra-AR hydrogen bonding involving the hydroxyl group; (2) the intra-AR and inter-AR hydrogen bonds involving the imidazole ring; and (3) the hydrophobic interaction associated with the Thr-methyl group. Considering that the capping and close-to-capping units tend to have more sequence diversity and more conformational variation, it could be also generally true that a T/SxxH motif close to the terminal repeats contributes little or even negatively to stability with respect to Ala substitution, but substantially stabilizes the global conformation when located in the middle of a long stretch of ARs. (C) 2010 Elsevier Ltd. All rights reserved.

语种英语
所属项目编号CA69472
资助者National Institutes of Health ; National Institutes of Health
WOS记录号WOS:000278779900014
Citation statistics
Cited Times:8[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/66557
Collection北京大学基础医学院_北京大学衰老研究中心
作者单位1.Ohio State Univ, Dept Biomed Informat, Columbus, OH 43210 USA
2.Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
3.Ohio State Univ, Dept Chem, Columbus, OH 43210 USA
4.Acad Sinica, Inst Biol Chem, Taipei, Taiwan
5.Acad Sinica, Genome Res Ctr, Taipei, Taiwan
6.Ohio State Univ, Div Environm Hlth Sci, Coll Publ Hlth, Columbus, OH 43210 USA
7.Ohio State Univ, Ohio State Biochem Program, Columbus, OH 43210 USA
8.Ohio State Univ, Campus Chem Instrument Ctr, Columbus, OH 43210 USA
9.Peking Univ, Hlth Sci Ctr, Res Ctr Aging, Dept Biochem & Mol Biol, Beijing 100871, Peoples R China
Recommended Citation
GB/T 7714
Guo, Yi,Yuan, Chunhua,Tian, Feng,et al. Contributions of Conserved TPLH Tetrapeptides to the Conformational Stability of Ankyrin Repeat Proteins[J]. JOURNAL OF MOLECULAR BIOLOGY,2010,399(1):168-181.
APA Guo, Yi.,Yuan, Chunhua.,Tian, Feng.,Huang, Kun.,Weghorst, Christopher M..,...&Li, Junan.(2010).Contributions of Conserved TPLH Tetrapeptides to the Conformational Stability of Ankyrin Repeat Proteins.JOURNAL OF MOLECULAR BIOLOGY,399(1),168-181.
MLA Guo, Yi,et al."Contributions of Conserved TPLH Tetrapeptides to the Conformational Stability of Ankyrin Repeat Proteins".JOURNAL OF MOLECULAR BIOLOGY 399.1(2010):168-181.
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