期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：14
页码：5026-5031
DOI：10.1073/pnas.0501372102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Using native-state hydrogen-exchange-directed protein engineering and multidimensional NMR, we determined the high-resolution structure (rms deviation, 1.1 A) for an intermediate of the four-helix bundle protein: Rd-apocytochrome b562. The intermediate has the N-terminal helix and a part of the C-terminal helix unfolded. In earlier studies, we also solved the structures of two other folding intermediates for the same protein: one with the N-terminal helix alone unfolded and the other with a reorganized hydrophobic core. Together, these structures provide a description of a protein folding pathway with multiple intermediates at atomic resolution. The two general features for the intermediates are (i) native-like backbone topology and (ii) nonnative side-chain interactions. These results have implications for important issues in protein folding studies, including large-scale conformation search, {phi}-value analysis, and computer simulations.
关键词：hidden folding intermediate ; native-state hydrogen exchange ; NMR structure ; protein engineering ; protein structure
