Contribution of hydrophobic interactions to protein stability.
Contribution of hydrophobic interactions to protein stability.
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DOI：
10.1016/j.jmb.2011.02.053
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发表时间：
2011-05-06
影响因子：
5.6
通讯作者：
Grimsley GR
中科院分区：
文献类型：
--
作者：
Pace CN;Fu H;Fryar KL;Landua J;Trevino SR;Shirley BA;Hendricks MM;Iimura S;Gajiwala K;Scholtz JM;Grimsley GR
我们的目标是更好地理解疏水相互作用对蛋白质稳定性的贡献。我们测量了四种疏水蛋白突变体的构象稳定性变化Δ（ΔG）：含有36个残基的绒毛蛋白头片段亚结构域（VHP），含有341个残基的伯氏疏螺旋体（VlsE）表面蛋白，以及我们实验室之前研究过的两种蛋白，核糖核酸酶Sa和T1。我们将我们的研究结果与以往的研究结果进行比较，得出以下结论。1. 疏水相互作用对小蛋白VHP（每- ch2 -基团0.6±0.3 kcal/mol）的稳定性贡献小于对大蛋白VlsE（每- ch2 -基团1.6±0.3 kcal/mol）的稳定性贡献。2. 疏水相互作用对VHP的稳定性（40 kcal/mol）起主要作用，主要作用因子为：Phe 18（3.9）、Met 13（3.1）、Phe 7（2.9）、Phe 11（2.7）和Leu 21（2.7）。3. 根据13种蛋白质中148个疏水突变体的Δ（ΔG）值，在折叠上埋一个- ch2 -基团对蛋白质稳定性的贡献平均为1.1±0.5 kcal/mol。4. 脂肪侧链（Ala, Val， Ile和Leu）的实验Δ（ΔG）值与从水到环己烷的ΔGtr值吻合良好。5. 对于含有36 ~ 534个残基的22种蛋白质，疏水相互作用对蛋白质稳定性的贡献为60±4%，氢键对蛋白质稳定性的贡献为40±4%。6. 构象熵对蛋白质不稳定性的影响约为每残基2.4千卡/摩尔。蛋白质的球状构象主要是通过疏水相互作用来稳定的。
Our goal was to gain a better understanding of the contribution of hydrophobic interactions to protein stability. We measured the change in conformational stability, Δ(ΔG), for hydrophobic mutants of four proteins: villin head piece subdomain (VHP) with 36 residues, a surface protein from Borrelia burgdorferi (VlsE) with 341 residues, and two proteins previously studied in our laboratory, ribonucleases Sa and T1. We compare our results with previous studies and reach the following conclusions. 1. Hydrophobic interactions contribute less to the stability of a small protein, VHP (0.6 ± 0.3 kcal/mole per –CH2– group), than to the stability of a large protein, VlsE (1.6 ± 0.3 kcal/mol per –CH2– group). 2. Hydrophobic interactions make the major contribution to the stability of VHP (40 kcal/mol) and the major contributors are (in kcal/mol): Phe 18 (3.9), Met 13 (3.1), Phe 7 (2.9), Phe 11 (2.7), and Leu 21 (2.7). 3. Based on Δ(ΔG) values for 148 hydrophobic mutants in 13 proteins, burying a –CH2– group on folding contributes, on average, 1.1 ± 0.5 kcal/mol to protein stability. 4. The experimental Δ(ΔG) values for aliphatic side chains (Ala, Val, Ile, and Leu) are in good agreement with their ΔGtr values from water to cyclohexane. 5. For 22 proteins with 36 to 534 residues, hydrophobic interactions contribute 60 ± 4% and hydrogen bonds 40 ± 4% to protein stability. 6. Conformational entropy contributes about 2.4 kcal/mol per residue to protein instability. The globular conformation of proteins is stabilized predominately by hydrophobic interactions.
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