Protein plasticity to the extreme:: changing the topology of a 4-α-helical bundle with a single amino acid substitution
Protein plasticity to the extreme:: changing the topology of a 4-α-helical bundle with a single amino acid substitution
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DOI：
10.1016/s0969-2126(99)80081-1
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发表时间：
1999-06-15
期刊：
影响因子：
5.7
通讯作者：
Kokkinidis, M
中科院分区：
文献类型：
--
作者：
Glykos, NM;Cesareni, G;Kokkinidis, M
背景：传统观点认为，两个具有98.4%序列同一性的蛋白质具有几乎相同的三维结构。在这里，我们提供了一个反例，通过显示单个氨基酸取代可以改变同源二聚体钙螺旋束蛋白的拓扑结构。结果：我们确定了一个4- α -螺旋蛋白的高分辨率晶体结构，该蛋白在翻转区发生了单丙氨酸到脯氨酸的突变，并表明这种单氨基酸取代导致整个分子的完全重组。该蛋白质由典型的左旋全反平行形式转化为右旋混合平行和反平行束，据我们所知和所相信，这代表了这类蛋白质的一种新的拓扑基序。结论：这些结果为拓扑基序的产生和进化提供了一种可能的新机制，显示了环区在决定允许折叠路径中的重要性，并说明了蛋白质结构的延展性。
Background: Conventional wisdom has it that two proteins sharing 98.4% sequence identity have nearly identical three-dimensional structures. Here we provide a counter-example to this statement by showing that a single amino acid substitution can change the topology of a homodimeric Ca-helical bundle protein.Results: We have determined the high-resolution crystal structure of a 4-alpha-helical protein with a single alanine to proline mutation in the turn region, and show that this single amino acid substitution leads to a complete reorganisation of the whole molecule. The protein is converted from the canonical left-handed all-antiparallel form, to a right-handed mixed parallel and antiparallel bundle, which to the best of our knowledge and belief represents a novel topological motif for this class of proteins.Conclusions: The results suggest a possible new mechanism for the creation and evolution of topological motifs, show the importance of loop regions in determining the allowable folding pathways, and illustrate the malleability of protein structures.