Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif
Plant cyclotides: A unique family of cyclic and knotted proteins that defines the cyclic cystine knot structural motif
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DOI：
10.1006/jmbi.1999.3383
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发表时间：
1999-12-17
影响因子：
5.6
通讯作者：
Waine, C
中科院分区：
文献类型：
--
作者：
Craik, DJ;Daly, NL;Waine, C
近年来，从茜草科和堇菜科植物中分离出了几种具有多种生物活性的大环肽（类似于30个氨基酸）。我们已经显着扩大了已知的大环肽的范围，发现了16种新的肽从常春藤科，紫花地丁和Oldenlandia affinis的提取物。以前没有对堇菜属植物进行过这些肽的检测，因此代表了产生这些不寻常的大环肽的新物种。此外，我们已经确定了这些新的肽之一，环紫素O 1的三维结构，使用H-1 NMR光谱。该结构由扭曲的三链β-折叠和二硫键的胱氨酸结排列组成。这种结构类似于kalata B1和circulin A，这是仅有的两种结构可用的大环肽，表明尽管整个肽的序列变异，但它们形成了一个家族，其中整体折叠是保守的。我们将这些肽称为环肽家族，将其嵌入拓扑结构称为环胱氨酸结（CCK）基序。这些分子独特的环状和打结性质使它们成为拓扑复杂蛋白质的一个迷人的例子。序列的检查显示，它们可以分为两个亚家族，其中一个往往含有大量的带正电荷的残基，并具有手镯样的骨架环化。第二个亚家族由于顺式-Pro肽键而含有骨架扭曲，并且在概念上可以被视为分子Moebius带。在这里，我们定义了CCK肽的两个明显的亚家族的结构特征，这可能是显着的，这些肽在植物中可能的防御相关的作用。(C)北京：科学出版社.
Several macrocyclic peptides (similar to 30 amino acids), with diverse biological activities, have been isolated from the Rubiaceae and Violaceae plant families over recent years. We have significantly expanded the range of known macrocyclic peptides with the discovery of 16 novel peptides from extracts of Viola hederaceae, Viola odorata and Oldenlandia affinis. The Viola plants had not previously been examined for these peptides and thus represent novel species in which these unusual macrocyclic peptides are produced. Further, we have determined the three-dimensional struc ture of one of these novel peptides, cycloviolacin O1, using H-1 NMR spectroscopy. The structure consists of a distorted triple-stranded beta-sheet and a cystine-knot arrangement of the disulfide bonds. This structure is similar to kalata B1 and circulin A, the only two macrocyclic peptides for which a structure was available, suggesting that despite the sequence variation throughout the peptides they form a family in which the overall fold is conserved. We refer to these peptides as the cyclotide family and their embedded topology as the cyclic cystine knot (CCK) motif. The unique cyclic and knotted nature of these molecules makes them a fascinating example of topologically complex proteins. Examination of the sequences reveals they can be separated into two subfamilies, one of which tends to contain a larger number of positively charged residues and has a bracelet-like circularization of the backbone. The second subfamily contains a backbone twist due to a cis-Pro peptide bond and may conceptually be regarded as a molecular Moebius strip. Here we define the structural features of the two apparent subfamilies of the CCK peptides which may be significant for the likely defense related role of these peptides within plants. (C) 1999 Academic Press.