A COMMON STRUCTURAL MOTIF INCORPORATING A CYSTINE KNOT AND A TRIPLE-STRANDED BETA-SHEET IN TOXIC AND INHIBITORY POLYPEPTIDES
A COMMON STRUCTURAL MOTIF INCORPORATING A CYSTINE KNOT AND A TRIPLE-STRANDED BETA-SHEET IN TOXIC AND INHIBITORY POLYPEPTIDES
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DOI：
10.1002/pro.5560031022
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发表时间：
1994-10-01
期刊：
影响因子：
8
通讯作者：
NORTON, RS
中科院分区：
文献类型：
--
作者：
PALLAGHY, PK;NIELSEN, KJ;NORTON, RS
通过比较多肽ω-芋螺毒素GVIA（Conus geographus）、kalata BI（Oldenlandia affinis DC）和CMTI-I（Curcurbita maxima）的三维结构，已经定义了由胱氨酸结和小的三链β-折叠组成的共同结构基序。这3种多肽具有不同的生物活性和可忽略的氨基酸序列同一性，但每种多肽均含有3个产生胱氨酸结的二硫键。该结由前2个键（1-4和2-5）和插入的多肽骨架形成的环组成，第三个二硫键（3-6）穿过该环。该基序的另一个组成部分是一个三链、反向平行β折叠，含有至少10个残基，XXC（2）、XC（5）X、XXC（6）X（其中半胱氨酸残基上的数字是指它们在二硫键模式中的位置）。在这些多肽中存在胱氨酸结和反平行β-折叠，这表明这两种结构特征都是基序稳定性所必需的。这种结构基序也存在于其他蛋白酶抑制剂和蜘蛛毒素中。它似乎是蛋白质中发现的最小的稳定球状结构域之一，通常用于毒素和抑制剂中，通过阻断较大蛋白质受体（如离子通道或蛋白酶）的功能发挥作用。
A common structural motif consisting of a cystine knot and a small triple-stranded beta-sheet has been defined from comparison of the 3-dimensional structures of the polypeptides omega-conotoxin GVIA (Conus geographus), kalata BI (Oldenlandia affinis DC), and CMTI-I (Curcurbita maxima). These 3 polypeptides have diverse biological activities and negligible amino acid sequence identity, but each contains 3 disulfide bonds that give rise to a cystine knot. This knot consists of a ring formed by the first 2 bonds (1-4 and 2-5) and the intervening polypeptide backbone, through which the third disulfide (3-6) passes. The other component of this motif is a triple-stranded, antiparallel beta-sheet containing a minimum of 10 residues, XXC(2), XC(5)X, XXC(6)X (where the numbers on the half-cystine residues refer to their positions in the disulfide pattern). The presence in these polypeptides of both the cystine knot and antiparallel beta-sheet suggests that both structural features are required for the stability of the motif. This structural motif is also present in other protease inhibitors and a spider toxin. It appears to be one of the smallest stable globular domains found in proteins and is commonly used in toxins and inhibitors that act by blocking the function of larger protein receptors such as ion channels or proteases.