New Tricks of an Old Pattern STRUCTURAL VERSATILITY OF SCORPION TOXINS WITH COMMON CYSTEINE SPACING
New Tricks of an Old Pattern STRUCTURAL VERSATILITY OF SCORPION TOXINS WITH COMMON CYSTEINE SPACING
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DOI：
10.1074/jbc.m111.329607
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发表时间：
2012-04-06
影响因子：
4.8
通讯作者：
del Rio-Portilla, Federico
中科院分区：
文献类型：
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作者：
Saucedo, Alma Leticia;Flores-Solis, David;del Rio-Portilla, Federico
蝎毒是K+通道阻断肽的丰富来源。在大多数情况下，它们是结构上相关的富含二硫键的小蛋白，含有六个半胱氨酸的保守模式，该模式被认为决定了它们共同的三维折叠。在传统模式中，两个二硫键将α螺旋片段连接到双链或三链β折叠的C末端链，从而形成胱氨酸稳定的α/β支架（CS α/β）。在这里，我们表明，两个K+通道阻断肽从天蝎座保存常见的蝎毒肽的半胱氨酸间距，但显示一个非常规的二硫键模式，伴随着一个完整的重排的二级结构拓扑结构到CS螺旋-环-螺旋折叠。采用这种新折叠的肽的序列和结构比较表明，它将是广泛的CS α/β支架的新阐述，从而揭示了这些富含二硫化物的小蛋白质的意想不到的结构多功能性。承认这种多功能性对于理解毒液结构复杂性如何出现在有限数量的分子支架上是很重要的。
Scorpion venoms are a rich source of K+ channel-blocking peptides. For the most part, they are structurally related small disulfide-rich proteins containing a conserved pattern of six cysteines that is assumed to dictate their common three-dimensional folding. In the conventional pattern, two disulfide bridges connect an alpha-helical segment to the C-terminal strand of a double- or triple-stranded beta-sheet, conforming a cystine-stabilized alpha/beta scaffold (CS alpha/beta). Here we show that two K+ channel-blocking peptides from Tityus scorpions conserve the cysteine spacing of common scorpion venom peptides but display an unconventional disulfide pattern, accompanied by a complete rearrangement of the secondary structure topology into a CS helix-loop-helix fold. Sequence and structural comparisons of the peptides adopting this novel fold suggest that it would be a new elaboration of the widespread CS alpha/beta scaffold, thus revealing an unexpected structural versatility of these small disulfide-rich proteins. Acknowledgment of such versatility is important to understand how venom structural complexity emerged on a limited number of molecular scaffolds.