Exploring symmetry as an avenue to the computational design of large protein domains.
Exploring symmetry as an avenue to the computational design of large protein domains.
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DOI：
10.1021/ja2051217
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发表时间：
2011-11-16
影响因子：
15
通讯作者：
Meiler, Jens
中科院分区：
文献类型：
--
作者：
Fortenberry, Cane;Bowman, Elizabeth Anne;Proffitt, Will;Dorr, Brent;Combs, Steven;Harp, Joel;Mizoue, Laura;Meiler, Jens
此前已经证明，对称的同源二聚体蛋白质在能量上受到青睐，这解释了它们在自然界中的丰度。利用Rosetta蛋白质设计软件对咪唑甘油磷酸合成酶(HISF)及其对应的对称同源二聚体的完全对称变体进行了计算设计。这种新的蛋白质被称为FLR，采用了对称的(βα)8提姆桶超级折叠。该蛋白质是可溶的、单体的，并表现出双重对称性，不仅在二级结构元素的排列上，而且在序列和原子细节上也被结晶学证实。当FLR被切成两半时，它很容易发生二聚，形成对称的同源二聚体。FLR的成功计算设计表明，我们在理解蛋白质稳定性的基本原理方面取得了进展，并为从较小片段构建较大蛋白质结构域提供了一种有吸引力的策略。
It was demonstrated previously that symmetric, homodimeric proteins are energetically favored, which explains their abundance in nature. It has been proposed that such symmetric homodimers underwent gene duplication and fusion to evolve into protein topologies that have a symmetric arrangement of secondary structure elements– “symmetric superfolds”.Here, the ROSETTA protein design software was used to computationally engineer a perfectly symmetric variant of imidazole glycerol phosphate synthase (HisF) and its corresponding symmetric homodimer. The new protein, termed FLR, adopts the symmetric (βα)8 TIM-barrel superfold. The protein is soluble, monomeric, and exhibits two-fold symmetry not only in the arrangement of secondary structure elements, but in sequence and at atomic detail as verified by crystallography. When cut in half, FLR dimerizes readily to form the symmetric homodimer. The successful computational design of FLR demonstrates progress in our understanding of the underlying principles of protein stability and presents an attractive strategy for the in silico construction of larger protein domains from smaller pieces.
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DOI：
10.1073/pnas.0405832101
发表时间：
2004-11-23
影响因子：
11.1
作者：
Hocker, B;Claren, J;Sterner, R
通讯作者：
Sterner, R
影响因子：
2.9
作者：
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通讯作者：
Sterner, Reinhard
DOI：
10.1073/pnas.93.25.14249
发表时间：
1996-12-10
影响因子：
11.1
作者：
Wolynes, PG
通讯作者：
Wolynes, PG
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影响因子：
14.9
作者：
Soeding, Johannes;Remmert, Michael;Biegert, Andreas
通讯作者：
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影响因子：
64.8
作者：
Levy, Emmanuel D.;Erba, Elisabetta Boeri;Robinson, Carol V.;Teichmann, Sarah A.
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Teichmann, Sarah A.