Schulman B A, Kim P S, Dobson C M, Redfield C
Howard Hughes Medical Institute, Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.
Nat Struct Biol. 1997 Aug;4(8):630-4. doi: 10.1038/nsb0897-630.
Molten globules are partially folded forms of proteins that are thought to be general intermediates in protein folding. Nonetheless, there is limited structural information about such species because they possess conformational heterogeneity and complex dynamical properties that lead to extreme line broadening in NMR spectra. Here we use a 2-D NMR approach that overcomes this difficulty by detecting the unfolding of individual residues in a molten globule in increasing concentrations of denaturant. The results show that the structure in the low pH form of alpha-lactalbumin (alpha-LA) is not formed cooperatively. Moreover, a core region remains collapsed under extremely denaturing conditions, even when the majority of the polypeptide chain is completely unfolded. Our results support a model for protein folding in which the core provides a template for correct assembly of the remainder of the structure.
熔球态是蛋白质的部分折叠形式，被认为是蛋白质折叠过程中的一般中间体。然而，关于这类物质的结构信息有限，因为它们具有构象异质性和复杂的动力学性质，这导致核磁共振谱线极度展宽。在此，我们采用二维核磁共振方法，通过检测在变性剂浓度增加时熔球态中单个残基的去折叠来克服这一困难。结果表明，α-乳白蛋白（α-LA）低pH形式的结构不是协同形成的。此外，即使大部分多肽链完全展开，在极端变性条件下核心区域仍保持折叠状态。我们的结果支持一种蛋白质折叠模型，即核心为结构其余部分的正确组装提供模板。
