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Oligomerization of a symmetric β‐trefoil protein in response to folding nucleus perturbation
- Source :
- Protein Sci
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Gene duplication and fusion events in protein evolution are postulated to be responsible for the common protein folds exhibiting internal rotational symmetry. Such evolutionary processes can also potentially yield regions of repetitive primary structure. Repetitive primary structure offers the potential for alternative definitions of critical regions, such as the folding nucleus (FN). In principle, more than one instance of the FN potentially enables an alternative folding pathway in the face of a subsequent deleterious mutation. We describe the targeted mutation of the carboxyl-terminal region of the (internally located) FN of the de novo designed purely-symmetric β-trefoil protein Symfoil-4P. This mutation involves wholesale replacement of a repeating trefoil-fold motif with a "blade" motif from a β-propeller protein, and postulated to trap that region of the Symfoil-4P FN in a nonproductive folding intermediate. The resulting protein (termed "Bladefoil") is shown to be cooperatively folding, but as a trimeric oligomer. The results illustrate how symmetric protein architectures have potentially diverse folding alternatives available to them, including oligomerization, when preferred pathways are perturbed.
- Subjects :
- Models, Molecular
Protein Folding
Full‐length Papers
Chemistry
Protein primary structure
Crystallography, X-Ray
Biochemistry
Oligomer
Protein evolution
Evolution, Molecular
chemistry.chemical_compound
medicine.anatomical_structure
Trefoil Factors
Targeted Mutation
Gene Duplication
Gene duplication
Biophysics
medicine
Protein Multimerization
Protein Structure, Quaternary
Molecular Biology
Deleterious mutation
Trefoil
Nucleus
Subjects
Details
- ISSN :
- 1469896X and 09618368
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- Protein Science
- Accession number :
- edsair.doi.dedup.....30ae432f384f0484a700e6003a3e863d