Identification of a key structural element for protein folding within beta-hairpin turns.
Identification of a key structural element for protein folding within beta-hairpin turns.
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DOI：
10.1016/s0022-2836(03)00321-8
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发表时间：
2003-05
影响因子：
5.6
通讯作者：
Jaewon Kim;S. Brych;Jihun Lee;T. Logan;M. Blaber
中科院分区：
文献类型：
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作者：
Jaewon Kim;S. Brych;Jihun Lee;T. Logan;M. Blaber
多肽中的特定残基可能是独特天然结构的稳定性和可折叠性的关键因素。因此，识别和预测这些残基是解决蛋白质折叠问题的一个重要研究领域。非典型的主链构象可以帮助识别折叠蛋白质中的菌株，并且通过推断，独特氨基酸可能由于对稳定性和折叠的有利贡献而具有天然高频率出现的位置。位于Ramachandran图的左手α-螺旋区（L-α）附近的非Gly残基是结构应变的潜在指标。虽然许多研究人员已经研究了在这些位置的突变，没有一致的能量或动力学的稳定性或折叠的贡献已经阐明。在这里，我们报告了一项研究，研究了在人酸性成纤维细胞生长因子内定义的β-发夹转角的特征位置的L-α区域内发现的Gly、Ala和Asn取代的影响，并证明了对稳定性和折叠动力学的一致影响。的热力学和动力学数据进行比较，在其他蛋白质中的类似突变的可用数据，具有良好的协议。结果已经确定，β-发夹转角子集内i+3位置处的Gly是增加多肽折叠至天然状态的速率同时保持解折叠速率基本不变的关键贡献者。
Specific residues in a polypeptide may be key contributors to the stability and foldability of the unique native structure. Identification and prediction of such residues is, therefore, an important area of investigation in solving the protein folding problem. Atypical main-chain conformations can help identify strains within a folded protein, and by inference, positions where unique amino acids may have a naturally high frequency of occurrence due to favorable contributions to stability and folding. Non-Gly residues located near the left-handed α-helical region (L-α) of the Ramachandran plot are a potential indicator of structural strain. Although many investigators have studied mutations at such positions, no consistent energetic or kinetic contributions to stability or folding have been elucidated. Here we report a study of the effects of Gly, Ala and Asn substitutions found within the L-α region at a characteristic position in defined β-hairpin turns within human acidic fibroblast growth factor, and demonstrate consistent effects upon stability and folding kinetics. The thermodynamic and kinetic data are compared to available data for similar mutations in other proteins, with excellent agreement. The results have identified that Gly at the i+3 position within a subset of β-hairpin turns is a key contributor towards increasing the rate of folding to the native state of the polypeptide while leaving the rate of unfolding largely unchanged.