Effect of proline and glycine residues on dynamics and barriers of loop formation in polypeptide chains
Effect of proline and glycine residues on dynamics and barriers of loop formation in polypeptide chains
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DOI：
10.1021/ja042798i
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发表时间：
2005-03-16
影响因子：
15
通讯作者：
Kiefhaber, T
中科院分区：
文献类型：
--
作者：
Krieger, F;Möglich, A;Kiefhaber, T
甘氨酸和脯氨酸残基经常在蛋白质的依次和环状结构中发现，并且被认为在折叠早期的链压缩过程中起重要作用。我们研究了它们对各种非结构化多肽链中链内环形成动力学的影响。与任何其他氨基酸相比，反式脯氨酰肽键周围的环形成明显较慢，甘氨酸残基周围的环形成更快。然而，短循环形成最快的顺式脯氨酰键周围的时间常数为6 ns的端到端的接触形成在一个四个残基的循环。短环的形成遇到15至30 kJ/mol范围内的活化能。甘氨酸和反式脯氨酰键周围的动力学改变可以主要归因于它们对活化能的影响。相反，顺式脯氨酰键周围的快速动力学起源于更高的Arrhenius指数前因子，其补偿了与反式异构体相比增加的环形成活化能。含脯氨酸的肽的全原子模拟表明，顺式脯氨酰异构体的构象空间在很大程度上受到限制相比，反式异构体。这导致平均末端到末端距离降低，并且顺式异构体中环形成后构象熵的损失较小。结果进一步表明，甘氨酸和脯氨酸残基仅影响含有2至10个残基的短环的形成，这是天然蛋白质中典型的环大小。较大环的形成不受单个甘氨酸或脯氨酸残基存在的影响。
Glycine and proline residues are frequently found in turn and loop structures of proteins and are believed to play an important role during chain compaction early in folding. We investigated their effect on the dynamics of intrachain loop formation in various unstructured polypeptide chains. Loop formation is significantly slower around trans prolyl peptide bonds and faster around glycine residues compared to any other amino acid. However, short loops are formed fastest around cis prolyl bonds with a time constant of 6 ns for end-to-end contact formation in a four-residue loop. Formation of short loops encounters activation energies in the range of 15 to 30 kJ/mol. The altered dynamics around glycine and trans prolyl bonds can be mainly ascribed to their effects on the activation energy. The fast dynamics around cis prolyl bonds, in contrast, originate in a higher Arrhenius pre-exponential factor, which compensates for an increased activation energy for loop formation compared to trans isomers. All-atom simulations of proline-containing peptides indicate that the conformational space for cis prolyl isomers is largely restricted compared to trans isomers. This leads to decreased average end-to-end distances and to a smaller loss in conformational entropy upon loop formation in cis isomers. The results further show that glycine and proline residues only influence formation of short loops containing between 2 and 10 residues, which is the typical loop size in native proteins. Formation of larger loops is not affected by the presence of a single glycine or proline residue.