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Ultrafast folding of α 3 D: A de novo designed three-helix bundle protein

2003; National Academy of Sciences; Volume: 100; Issue: 26 Linguagem: Inglês

10.1073/pnas.2136623100

1091-6490

Yongjin Zhu, Darwin O. V. Alonso, Kosuke Maki, Cheng‐Yen Huang, Steven J. Lahr, Valerie Daggett, Heinrich Röder, William F. DeGrado, Feng Gai,

Hemoglobin structure and function

Here, we describe the folding/unfolding kinetics of α 3 D, a small designed three-helix bundle. Both IR temperature jump and ultrafast fluorescence mixing methods reveal a single-exponential process consistent with a minimal folding time of 3.2 ± 1.2 μs (at ≈50°C), indicating that a protein can fold on the 1- to 5-μs time scale. Furthermore, the single-exponential nature of the relaxation indicates that the prefactor for transition state (TS)-folding models is probably ≥1 (μs) –1 for a protein of this size and topology. Molecular dynamics simulations and IR spectroscopy provide a molecular rationale for the rapid, single-exponential folding of this protein. α 3 D shows a significant bias toward local helical structure in the thermally denatured state. The molecular dynamics-simulated TS ensemble is highly heterogeneous and dynamic, allowing access to the TS via multiple pathways.