Work

The Fast and the Slow: Folding and Trapping of λ6–85

Year: 2011

Type: article

Abstract: Molecular dynamics simulations combining many microsecond trajectories have recently predicted that a very fast folding protein like lambda repressor fragment λ(6-85) D14A could have a slow millisecond kinetic phase. We investigated this possibility by detecting temperature-jump relaxation to 5 ms. While λ(6-85) D14A has no significant slow phase, two even more stable mutants do. A slow phase of λ(6-85) D14A does appear in mild denaturant. The experimental data and computational modeling together suggest the following hypothesis: λ(6-85) takes only microseconds to reach its native state from an extensively unfolded state, while the latter takes milliseconds to reach compact β-rich traps. λ(6-85) is not only thermodynamically but also kinetically protected from reaching such "intramolecular amyloids" while folding.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja209073z

Authors: Maxim B. Prigozhin, Martin Gruebele

Institution: University of Illinois Urbana-Champaign

Language: English

Topic: Protein Structure and Dynamics

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences

Awards: G3425486910, Protein domains interacting with crowders, RNA and other protein domains