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Folding Nucleus Structure Persists in Thermally-Aggregated FGF-1

Title: The Folding Nucleus Structure Persists in Thermally-Aggregated FGF-1.
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Name(s): Longo, Liam, author
Gao, Yuan, author
Tenorio, Connie, author
Wang, Gan, author
Paravastu, Anant, author
Blaber, Michael, author
Type of Resource: text
Genre: Text
Journal Article
Date Issued: 2017-10-23
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: An efficient protein folding pathway leading to target structure, and the avoidance of aggregation, is essential to protein evolution and de novo design; however, design details to achieve efficient folding and avoid aggregation are poorly understood. We report characterization of the thermally-induced aggregate of fibroblast growth factor-1 (FGF-1), a small globular protein, by solid-state NMR. NMR spectra are consistent with residual structure in the aggregate and provide evidence of a structured region that corresponds to the region of the folding nucleus. NMR data on aggregated FGF-1 also indicate the presence of unstructured regions that exhibit hydration-dependent dynamics and suggest that unstructured regions of aggregated FGF-1 lie outside the folding nucleus. Since it is known that regions outside the folding nucleus fold late in the folding pathway, we postulate that these regions unfold early in the unfolding pathway and that the partially folded state is more prone to intermolecular aggregation. This interpretation is further supported by comparison with a designed protein that shares the same FGF-1 folding nucleus sequence, but has different 1° structure outside the folding nucleus, and does not thermally aggregate. The results suggest that design of an efficient folding nucleus, and the avoidance of aggregation in the folding pathway, are potentially separable design criteria – the latter of which could principally focus upon the physicochemical properties of 1° structure outside the folding nucleus.
Identifier: FSU_libsubv1_scholarship_submission_1509376995_85b5a7ca (IID), 10.1002/pro.3332 (DOI)
Keywords: Misfolding, Folding pathway, Protein design, Protein evolution, Biophysics, Thermodynamics, Solid-state NMR, De novo design
Publication Note: Uncorrected accepted version made available online Oct 23 2017. The final published version of this article can be found at http://www.doi.org/10.1002/pro.3332.
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1509376995_85b5a7ca
Owner Institution: FSU
Is Part Of: Protein Science.

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Longo, L., Gao, Y., Tenorio, C., Wang, G., Paravastu, A., & Blaber, M. (2017). The Folding Nucleus Structure Persists in Thermally-Aggregated FGF-1. Protein Science. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1509376995_85b5a7ca