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Evolution of a Protein Folding Nucleus

Title: Evolution of a Protein Folding Nucleus.
Name(s): Xia, Xue, author
Longo, Liam M., author
Sutherland, Mason A., author
Blaber, Michael, author
Type of Resource: text
Genre: Text
Date Issued: 2015-12-10
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: The folding nucleus (FN) is a cryptic element within protein primary structure that enables an efficient folding pathway and is the postulated heritable element in the evolution of protein architecture; however, almost nothing is known regarding how the FN structurally changes as complex protein architecture evolves from simpler peptide motifs. We report characterization of the FN of a designed purely symmetric β-trefoil protein by ϕ-value analysis. We compare the structure and folding properties of key foldable intermediates along the evolutionary trajectory of the β-trefoil. The results show structural acquisition of the FN during gene fusion events, incorporating novel turn structure created by gene fusion. Furthermore, the FN is adjusted by circular permutation in response to destabilizing functional mutation. FN plasticity by way of circular permutation is made possible by the intrinsic C3 cyclic symmetry of the β-trefoil architecture, identifying a possible selective advantage that helps explain the prevalence of cyclic structural symmetry in the proteome.
Identifier: FSU_libsubv1_scholarship_submission_1464367133 (IID), 10.1002/pro.2848 (DOI), PMC4918426 (PMCID)
Keywords: Protein design, β-trefoil, Phi-value, Folding transition state, Folding pathway
Publication Note: The publisher's version of this article is available at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Preferred Citation: Xia, X., Longo, L. M., Sutherland, M. A. and Blaber, M. (2016), Evolution of a protein folding nucleus. Protein Science, 25: 1227–1240. doi:10.1002/pro.2848
Persistent Link to This Record:
Owner Institution: FSU
Is Part Of: Protein Science.
Issue: iss. 7, vol. 25

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Xia, X., Longo, L. M., Sutherland, M. A., & Blaber, M. (2015). Evolution of a Protein Folding Nucleus. Protein Science. Retrieved from