Long-range interactions within a nonnative protein
Long-range interactions within a nonnative protein
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DOI：
10.1126/science.1067680
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发表时间：
2002-03-01
期刊：
影响因子：
56.9
通讯作者：
Schwalbe, H
中科院分区：
文献类型：
--
作者：
Klein-Seetharaman, J;Oikawa, M;Schwalbe, H
蛋白质折叠和解折叠与一系列生物现象相关联，从细胞活性的调节到神经退行性疾病的发作。定义非天然蛋白质中采样的构象的性质对于理解这种现象的起源至关重要。我们已经使用了核磁共振（NMR）光谱和定点诱变相结合，研究蛋白质溶菌酶的未折叠状态。即使在强变性条件下，野生型蛋白质内也存在广泛的疏水结构簇。这些簇涉及序列的不同区域，但都被单个点突变破坏，该点突变将位于天然状态下两个主要结构域界面处的残基Trp（62）替换为Gly。因此，变性蛋白质中的类天然结构通过Trp（62）参与非天然和长程相互作用而稳定。
Protein folding and unfolding are coupled to a range of biological phenomena, from the regulation of cellular activity to the onset of neurodegenerative diseases. Defining the nature of the conformations sampled in nonnative proteins is crucial for understanding the origins of such phenomena. We have used a combination of nuclear magnetic resonance (NMR) spectroscopy and site-directed mutagenesis to study unfolded states of the protein lysozyme. Extensive clusters of hydrophobic structure exist within the wild-type protein even under strongly denaturing conditions. These clusters involve distinct regions of the sequence but are all disrupted by a single point mutation that replaced residue Trp(62) with Gly located at the interface of the two major structural domains in the native state. Thus, nativelike structure in the denatured protein is stabilized by the involvement of Trp(62) in nonnative and long-range interactions.