Intermediates and the folding of proteins L and G |
| |
Authors: | Brown Scott Head-Gordon Teresa |
| |
Institution: | Department of Bioengineering, 472 Donner Laboratory, University of California, Berkeley, Berkeley, CA 94720-1762, USA. |
| |
Abstract: | We use a minimalist protein model, in combination with a sequence design strategy, to determine differences in primary structure for proteins L and G, which are responsible for the two proteins folding through distinctly different folding mechanisms. We find that the folding of proteins L and G are consistent with a nucleation-condensation mechanism, each of which is described as helix-assisted beta-1 and beta-2 hairpin formation, respectively. We determine that the model for protein G exhibits an early intermediate that precedes the rate-limiting barrier of folding, and which draws together misaligned secondary structure elements that are stabilized by hydrophobic core contacts involving the third beta-strand, and presages the later transition state in which the correct strand alignment of these same secondary structure elements is restored. Finally, the validity of the targeted intermediate ensemble for protein G was analyzed by fitting the kinetic data to a two-step first-order reversible reaction, proving that protein G folding involves an on-pathway early intermediate, and should be populated and therefore observable by experiment. |
| |
Keywords: | intermediates kinetic mechanism protein L and G minimalist model protein folding |
本文献已被 PubMed 等数据库收录! |
|