Spotlights on Recent JACS Publications.

作者：Sarah Anderson · 发表于：Journal of the American Chemical Society · 年份：2020 · DOI：10.1021/jacs.0c00435 · 研究领域：Medicine

To adopt the unique structure that dictates its function, a protein must fold into its active conformation. While traditional thinking holds that the process of folding occurs through a single pathway for each protein, there is growing evidence that the same folded protein can be arrived at by several distinct routes. However, a shortage of studies that rigorously characterize parallel protein folding pathways has left this matter unresolved within the scientific community. Now, Jayant B. Udgaonkar and colleagues provide an indepth structural analysis of the multiple folding pathways that yield the monellin-derived protein MNEI (DOI: 10.1021/ jacs.0c11097). The researchers created four versions of MNEI with a fluorescent donor and acceptor pair installed at different sites and measured distant-dependent energy transfer over time to track the protein’s structural features as it transitioned from an unfolded to a folded state. They found that MNEI first exists as a “collapsed ensemble” that, while unfolded overall, contains subregions of structural definition. The protein then diverges into four separate pathways in which individual segments fold at various times and through diverse mechanisms. In averaging the four pathways, the team observed that local features are formed before global protein structure is finalized, with α helix formation, core consolidation, and β-sheet formation preceding end-to-end protein distance reduction. As MNEI is commonly used as a model in protein...