A tale of two secondary structure elements: when a beta-hairpin becomes an alpha-helix.
A tale of two secondary structure elements: when a beta-hairpin becomes an alpha-helix.
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两个二级结构元素的故事：当β-发夹变成α-螺旋时。
DOI：
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发表时间：
1999
影响因子：
5.6
通讯作者：
Luis Serrano
中科院分区：
文献类型：
--
作者：
D. Cregut;C. Civera;Maria J. Macias;Gerlind Wallon;Luis Serrano
在这项工作中，我们分析了二级与三级相互作用在稳定和指导蛋白质折叠方面的相对重要性。为此，我们设计了四种不同的突变体，用具有强β发夹倾向的序列单独替换GB1结构域的α螺旋。特别是，我们选择了 GB1 结构域的第二个 β-发夹的序列，它在很大程度上填充了水溶液中的天然构象。所得蛋白质大约有 30% 的序列重复，并保持野生型蛋白质的 3D 结构，但稳定性较低（高达 -5 kcal/mol）。内在螺旋稳定性的丧失约占自由能减少的 80%，这说明了局部相互作用在蛋白质稳定性中的重要性。有趣的是，所有突变蛋白，包括具有重复 β-发夹序列的突变蛋白，都以与 GB1 结构域相似的速率折叠。本质上，折叠反应中限速步骤的性质决定了特定的相互作用是否会加速折叠速率。虽然局部接触对于确定蛋白质稳定性很重要，但参与三级接触的残基与天然折叠的拓扑结构相结合，似乎决定了蛋白质结构的特异性。具有非天然二级结构倾向的蛋白质可以采用稳定的折叠，并且与具有类似天然倾向的蛋白质一样有效地折叠。
In this work, we have analyzed the relative importance of secondary versus tertiary interactions in stabilizing and guiding protein folding. For this purpose, we have designed four different mutants to replace the alpha-helix of the GB1 domain by a sequence with strong beta-hairpin propensity in isolation. In particular, we have chosen the sequence of the second beta-hairpin of the GB1 domain, which populates the native conformation in aqueous solution to a significant extent. The resulting protein has roughly 30 % of its sequence duplicated and maintains the 3D-structure of the wild-type protein, but with lower stability (up to -5 kcal/mol). The loss of intrinsic helix stability accounts for about 80 % of the decrease in free energy, illustrating the importance of local interactions in protein stability. Interestingly enough, all the mutant proteins, included the one with the duplicated beta-hairpin sequence, fold with similar rates as the GB1 domain. Essentially, it is the nature of the rate-limiting step in the folding reaction that determines whether a particular interaction will speed up, or not, the folding rates. While local contacts are important in determining protein stability, residues involved in tertiary contacts in combination with the topology of the native fold, seem to be responsible for the specificity of protein structures. Proteins with non-native secondary structure tendencies can adopt stable folds and be as efficient in folding as those proteins with native-like propensities.
影响因子：
2.9
作者：
ALEXANDER, P;FAHNESTOCK, S;BRYAN, P
通讯作者：
BRYAN, P
G 蛋白 B1 结构域折叠反应的早期中间体含有类似天然的核心。
DOI：
10.1021/bi971914
发表时间：
1997
期刊：
Biochemistry.
影响因子：
--
作者：
Park,SH;O'Neil,KT;Roder,H
通讯作者：
Roder,H
影响因子：
2.9
作者：
GILL, SC;VONHIPPEL, PH
通讯作者：
VONHIPPEL, PH