The folding pathway of T4 lysozyme: the high-resolution structure and folding of a hidden intermediate.

ABSTRACT: Folding intermediates have been detected and characterized for many proteins. However, their structures at atomic resolution have only been determined for two small single domain proteins: Rd-apocytochrome b(562) and engrailed homeo domain. T4 lysozyme has two easily distinguishable but energetically coupled domains: the N and C-terminal domains. An early native-state hydrogen exchange experiment identified an intermediate with the C-terminal domain folded and the N-terminal domain unfolded. We have used a native-state hydrogen exchange-directed protein engineering approach to populate this intermediate and demonstrated that it is on the folding pathway and exists after the rate-limiting step. Here, we determined its high-resolution structure and the backbone dynamics by multi-dimensional

SUBMITTER: Kato H 

PROVIDER: S-EPMC2494534 | biostudies-literature | 2007 Jan

REPOSITORIES: biostudies-literature