FURTHER-STUDIES OF THE HELIX DIPOLE MODEL - EFFECTS OF A FREE ALPHA-NH3+ OR ALPHA-COO- GROUP ON HELIX STABILITY
FURTHER-STUDIES OF THE HELIX DIPOLE MODEL - EFFECTS OF A FREE ALPHA-NH3+ OR ALPHA-COO- GROUP ON HELIX STABILITY
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DOI：
10.1002/prot.340050102
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发表时间：
1989-01-01
影响因子：
2.9
通讯作者：
BALDWIN, RL
中科院分区：
文献类型：
--
作者：
FAIRMAN, R;SHOEMAKER, KR;BALDWIN, RL
之间的相互作用。-螺旋肽偶极子和靠近螺旋末端的带电基团被发现是- α的重要决定因素。-螺旋稳定性在先前的研究中。核糖核酸酶A的c肽n端残基上的电荷主要通过改变。α而改变。-NH2阻断基团，并证明了螺旋稳定性与n端电荷的相关性。对其中一些结果的另一种解释是，琥珀基和乙酰基阻断基团通过与不满足的主链NH基团形成氢键来稳定螺旋。螺旋偶极子模型在这里用含有游离α的肽进行测试。-NH3+或。- coo -基团，没有其他带电基团会用类似的pKa' s滴定。这个模型预测。-NH3+和。- coo -基团是螺旋不稳定的，不稳定相互作用起源于静电。氢键模型预测。-NH3+和。- coo -基团本身并不破坏螺旋稳定，而是在N端或c端分别存在乙酰基或酰胺阻断基团，通过与不满足的主链NH或CO基团形成氢键来稳定螺旋。结果如下：(1). α的电荷去除。-NH3+和。- coo -基团通过pH滴定稳定α -螺旋。(2)这些基团在pH滴定时螺旋稳定性的增加与加入乙酰基或酰胺阻断基所产生的增加接近。(3)去除α中电荷的螺旋稳定效应。-NH3+和。通过pH滴定筛选- coo -基团是通过增加NaCl浓度来实现的，因此其作用的根源是静电。(4)用不能提供氢键的甲基酯阻断基取代c端酰胺阻断基，对螺旋稳定性影响不大。
Interactions between the .alpha.-helix peptide dipoles and charged groups close to the ends of the helix were found to be an important determinant of .alpha.-helix stability in a previous study. The charge on the N-terminal residue of the C-peptide from ribonuclease A was varied chiefly by changing the .alpha.-NH2 blocking group, and the correlation of helix stability with N-terminal charge was demonstrated. An alternative explanation for some of those results is that the succinyl and acetyl blocking groups stabilize the helix by hydrogen bonding to an unsatisfied main-chain NH group. The helix dipole model is tested here with peptides that contain either a free .alpha.-NH3+ or .alpha.-COO- group, and no other charged groups that would titrate with similar pKa''s. This model predicts that .alpha.-NH3+ and .alpha.-COO- groups are helix-destabilizing and that the destabilizing interactions are electrostatic in origin. The hydrogen bonding model predicts that .alpha.-NH3+ and .alpha.-COO- groups are not themselves helix-destabilizing, but that an acetyl or amide blocking group at the N- or C-terminus, respectively, stabilizes the helix by hydrogen bonding to an unsatisfied main-chain NH or CO group. The results are as follws: (1) Removal of the charge from .alpha.-NH3+ and .alpha.-COO- groups by pH titration stabilizes an .alpha.-helix. (2) The increase in helix stability on pH titration of these groups is close to the increase produced by adding an acetyl or amide blocking group. (3) The helix-stabilizing effect of removing the charge from .alpha.-NH3+ and .alpha.-COO- groups by pH titration is screened by increasing the NaCl concentration, and therefore the effect is electrostatic in origin. (4) Replacing the C-terminal amide blocking group with a methyl-ester blocking group, which cannot donate a hydrogen bond, causes little change in helix stability.