Underexposed polar residues and protein stabilization
Underexposed polar residues and protein stabilization
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DOI：
10.1093/protein/gzq072
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发表时间：
2011-01-01
影响因子：
2.4
通讯作者：
Sancho, Javier
中科院分区：
文献类型：
--
作者：
Ayuso-Tejedor, Sara;Abian, Olga;Sancho, Javier
提高蛋白质的稳定性是很有趣的，因为它测试了我们对蛋白质能量学的理解。我们在这里探讨了用类似大小和形状的极性残基取代暴露不足的极性残基来稳定蛋白质的可行性。我们已经比较了野生型阿黄氧多素与一些精心挑选的携带Y - >f、Q -> L、T - >v或K - >m替代品的突变体的稳定性。虽然观察到被取代的极性残基的天然溶剂暴露与突变体的稳定性之间存在明显的负相关，但大多数突变都不能稳定蛋白质。有希望的例外是测试的两个Q -> L突变，其特征是相对于野生型，极性埋葬的最大减少和极性埋葬的最大增加。对已发表的各种突变蛋白稳定性数据的分析证实，与Y - >f或T -> V替代不同，Q - >l突变趋于稳定，这表明N - >l突变也可能趋于稳定。另一方面，我们表明，与apoflavodoxin突变相关的稳定性变化可以通过折叠时的极性和极性差异埋葬加上一般的不稳定惩罚项来合理化。结合这些贡献的简单方程预测了113个突变体（Y - >f, Q -> L或T - >v）的大型数据集的稳定性变化，类似于互联网上更复杂的算法。
Increasing protein stability is interesting for practical reasons and because it tests our understanding of protein energetics. We explore here the feasibility of stabilizing proteins by replacing underexposed polar residues by apolar ones of similar size and shape. We have compared the stability of wild-type apoflavodoxin with that of a few carefully selected mutants carrying Y -> F, Q -> L, T -> V or K -> M replacements. Although a clear inverse correlation between native solvent exposures of replaced polar residues and stability of mutants is observed, most mutations fail to stabilize the protein. The promising exceptions are the two Q -> L mutations tested, which characteristically combine the greatest reduction in polar burial with the greatest increase in apolar burial relative to wild type. Analysis of published stability data corresponding to a variety of mutant proteins confirms that, unlike Y -> F or T -> V replacements, Q -> L mutations tend to be stabilizing, and it suggests that N -> L mutations might be stabilizing as well. On the other hand, we show that the stability changes associated to the apoflavodoxin mutations can be rationalized in terms of differential polar and apolar burials upon folding plus a generic destabilizing penalty term. Simple equations combining these contributions predict stability changes in a large data set of 113 mutants (Y -> F, Q -> L or T -> V) similarly well as more complex algorithms available on the Internet.