Amino acid bulkiness defines the local conformations and dynamics of natively unfolded α-synuclein and tau
Amino acid bulkiness defines the local conformations and dynamics of natively unfolded α-synuclein and tau
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DOI：
10.1021/ja067482k
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发表时间：
2007-03-21
影响因子：
15
通讯作者：
Zweckstetter, Markus
中科院分区：
文献类型：
--
作者：
Cho, Min-Kyu;Kim, Hai-Young;Zweckstetter, Markus
天然未折叠蛋白在正常和病理生化过程中起着关键作用。然而，这类蛋白质由于其固有的构象异质性，仍然超出了经典结构生物学的范围。当被限制在弱排列介质中时，天然未折叠的蛋白质，如α -突触核蛋白，帕金森病患者大脑中异常聚集体的主要成分，显示出令人惊讶的变化核磁共振偶极偶联，作为沿链位置的函数，表明存在残留的二级或三级结构。研究表明，α -突触核蛋白的核磁共振偶极偶联和异核弛豫速率的变化与多肽链上氨基酸的体积变化密切相关。我们的研究结果表明，氨基酸的体积决定了α -突触核蛋白和其他天然未折叠蛋白的局部构象和动力学。偏离这种随机线圈行为可以提供对未折叠蛋白质中残余二级结构和远程瞬时相互作用的见解。
Natively unfolded proteins play key roles in normal and pathological biochemical processes. This category of proteins remains, however, beyond the reach of classical structural biology because of their inherent conformational heterogeneity. When confined in weakly aligning media, natively unfolded proteins such as alpha-synuclein, the major component of abnormal aggregates in the brain of patients with Parkinson's disease, display surprisingly variable NMR dipolar couplings as a function of position along the chain, suggesting the presence of residual secondary or tertiary structure. Here we show that the variation of NMR dipolar couplings and heteronuclear relaxation rates in alpha-synuclein closely follows the variations of the bulkiness of amino acids along the polypeptide chain. Our results demonstrate that the bulkiness of amino acids defines the local conformations and dynamics of alpha-synuclein and other natively unfolded proteins. Deviations from this random coil behavior can provide insight into residual secondary structure and long-range transient interactions in unfolded proteins.