ELECTROSTATIC INTERACTIONS IN COLLAGEN-LIKE TRIPLE-HELICAL PEPTIDES
ELECTROSTATIC INTERACTIONS IN COLLAGEN-LIKE TRIPLE-HELICAL PEPTIDES
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DOI：
10.1021/bi00191a023
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发表时间：
1994-06-28
期刊：
影响因子：
2.9
通讯作者：
BRODSKY, B
中科院分区：
文献类型：
--
作者：
VENUGOPAL, MG;RAMSHAW, JAM;BRODSKY, B
研究了具有离子对形成潜力的胶原样肽，以探讨静电相互作用在三螺旋构象中的作用。三种肽-（POG）（10）、含EK的肽（POG）（4）EKG（POG）（5）和T3-487，一种具有18个III型胶原残基和C-末端（C-terminal）（4）尾的肽-都在水溶液中形成稳定的三股螺旋，其解链温度分别为58、46和26 ℃，这些肽的热稳定性与它们的亚氨基酸含量相关，亚氨基酸含量分别为66%、60%和41%。pH在1-13范围内的变化导致含EK的肽和肽T3-487的T-m发生8-9 ℃的变化，在酸性和碱性残基都被离子化的pH值下观察到最大的稳定性。平衡超离心显示这些肽在低温下主要是三聚体，没有六聚体或较大的聚集体，表明pH依赖性稳定性来自分子内相互作用。计算机模拟表明，链内离子对和链间离子对都可以形成并稳定三股螺旋。对（POG）（10）和T3-487的N-末端乙酰化形式的热稳定性的pH依赖性的研究表明，三个带电荷的N-末端或C-末端的排斥具有不稳定效应。考虑到这些末端效应，三螺旋中两个带相反电荷的残基的能量贡献为0.5-1千卡/摩尔离子对，这两个残基在空间上能够参与离子对和骨架氢键。离子对的稳定作用可能是间接产生的，通过消除相同电荷的排斥、形成单链形式的离子对或溶剂效应。
Collagen-like peptides with potential for ion pair formation were studied to investigate the role of electrostatic interactions in the triple-helix conformation. Three peptides-(POG)(10), the EK-containing peptide (POG)(4)EKG(POG)(5), and T3-487, a peptide with 18 residues of type III collagen and a C-terminal (GPO)(4) tail-all form stable triple helices in aqueous solution, with melting temperatures of 58, 46, and 26 degrees C, respectively, at neutral pH. The thermal stabilities of these peptides correlate with their imino acid content, which is 66%, 60%, and 41%, respectively. Variation of pH over the range of 1-13 led to 8-9 degrees C changes in the T-m of the EK-containing peptide and peptide T3-487, with the greatest stability seen at pH values where both acidic and basic residues are ionized. Equilibrium ultracentrifugation shows these peptides are largely trimeric at low temperature, with no hexamers or larger aggregates, indicating that the pH-dependent stability arises from intramolecular interaction. Computer modeling indicates both intrachain ion pairs and interchain ion pairs can form and stabilize the triple helix. Studies of the pH dependence of the thermal stability of (POG)(10) and the N-terminal acetylated form of T3-487 indicate that repulsion of the three charged N-terminal or C-terminal ends has a destabilizing effect. Taking into account these end effects, the energy contribution of two oppositely charged residues in a triple helix which are sterically capable of participating in ion pairs and backbone hydrogen bonding is 0.5-1 kcal/mol ion pair. It is possible that the stabilizing influence of ion pairs arises indirectly, through elimination of like charge repulsion, formation of ion pairs in the single chain form, or solvent effects.