Chemical synthesis of Arabidopsis CLV3 glycopeptide reveals the impact of hydroxyproline arabinosylation on peptide conformation and activity.
Chemical synthesis of Arabidopsis CLV3 glycopeptide reveals the impact of hydroxyproline arabinosylation on peptide conformation and activity.
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DOI：
10.1093/pcp/pcs174
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发表时间：
2013-03
影响因子：
4.9
通讯作者：
Matsubayashi Y
中科院分区：
文献类型：
--
作者：
Shinohara H;Matsubayashi Y
羟脯氨酸阿拉伯糖基化(Hyp)是一种翻译后修饰，常见于植物分泌肽信号中。CLAVATA3(ClV3)是调节拟南芥顶端分生组织中干细胞命运的关键多肽信号，它含有三个通过线性β-1，2-键连接的L阿拉伯糖残基，这一发现突显了这种修饰的生理意义。然而，合成复杂的阿拉伯糖链的困难阻碍了人们对阿拉伯糖基化多肽的功能和性质的了解。在这里，我们报道了立体选择性全合成β-1，2-连接的三阿拉伯糖基化的CLV3多肽([Ara3]CLV3)。化学合成的[Ara3]CLV3比未修饰的CLV3肽更有效地限制干细胞活性。比较单、二和三阿拉伯糖基化的CLV3糖肽，发现其生物活性随着阿拉伯糖链长度的增加而递增。因此，CLV3的阿拉伯糖链长度对其生物活性很重要。核磁共振波谱和基于核Overhauser效应的结构计算进一步揭示了阿拉伯糖链对多肽构象的结构影响。[Ara3]CLV3的阿拉伯糖链朝向多肽的C末端延伸，其非还原末端位于多肽骨架的近端。因此，阿拉伯糖链以高度定向的方式在多肽的C-末端半部分引起明显的扭曲。所建立的[Ara3]CLV3的合成路线将极大地有助于我们理解植物中阿拉伯糖基化多肽信号的生物学和生物化学。
Arabinosylation of hydroxyproline (Hyp) is a post-translational modification often found in secreted peptide signals in plants. The physiological importance of this modification was highlighted by the finding that CLAVATA3 (CLV3), a key peptide signal for regulating the fate of stem cells in the shoot apical meristem in Arabidopsis, contains three l-arabinose residues linked via linear β-1,2-linkages. However, understanding the functions and properties of arabinosylated peptides has been hindered by difficulties in synthesizing the complex arabinose chain. Here we report the stereoselective total synthesis of β-1,2-linked triarabinosylated CLV3 peptide ([Ara3]CLV3). Chemically synthesized [Ara3]CLV3 restricted stem cell activity more effectively than did unmodified CLV3 peptide. Comparison of mono-, di- and triarabinosylated CLV3 glycopeptides revealed that the biological activity increased progressively as the arabinose chain length increased. Thus, the arabinose chain length of CLV3 is important for its biological activity. Nuclear magnetic resonance spectroscopy and nuclear Overhauser effect-based structure calculations further revealed the structural impact of the arabinose chain on peptide conformation. The arabinose chain of [Ara3]CLV3 extends toward the C-terminal end of the peptide, and its non-reducing end is positioned proximal to the peptide backbone. Consequently, the arabinose chain causes distinct distortion in the C-terminal half of the peptide in a highly directional manner. The established synthetic route of [Ara3]CLV3 will greatly contribute to our understanding of the biology and biochemistry of arabinosylated peptide signals in plants.
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影响因子：
56.9
作者：
Fletcher, LC;Brand, U;Meyerowitz, EM
通讯作者：
Meyerowitz, EM
DOI：
10.1107/s0907444998003254
发表时间：
1998-09-01
期刊：
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY
影响因子：
--
作者：
Brunger, AT;Adams, PD;Warren, GL
通讯作者：
Warren, GL
DOI：
10.1073/pnas.0706403104
发表时间：
2007-11-13
影响因子：
11.1
作者：
Amano, Yukari;Tsubouchi, Hiroko;Matsubayashi, Yoshikatsu
通讯作者：
Matsubayashi, Yoshikatsu
影响因子：
7.4
作者：
LAMPORT, DTA;MILLER, DH
通讯作者：
MILLER, DH
影响因子：
4.8
作者：
Nitz, M;Ling, CC;Bundle, DR
通讯作者：
Bundle, DR