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Ab initio Folding of a Trefoil-fold Motif Reveals Structural similarity with a β-propeller Blade Motif

Title: Ab initio Folding of a Trefoil-fold Motif Reveals Structural similarity with a β-propeller Blade Motif.
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Name(s): Tenorio, Connie, author
Longo, Liam, author
Parker, Joseph, author
Lee, Jihun, author
Blaber, Michael, author
Type of Resource: text
Genre: Text
Journal Article
Date Issued: 2020-03-03
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Many protein architectures exhibit evidence of internal rotational symmetry postulated to be the result of gene duplication/fusion events involving a primordial polypeptide motif. A common feature of such structures is a domain-swapped arrangement at the interface of the N- and C-termini motifs and postulated to provide cooperative interactions that promote folding and stability. De novo designed symmetric protein architectures have demonstrated an ability to accommodate circular permutation of the N- and C-termini in the overall architecture; however, the folding requirement of the primordial motif are poorly understood, and tolerance to circular permutation is essentially unknown. The β-trefoil protein fold is a threefold symmetric architecture where the repeating ~42-mer “trefoil-fold” motif assembles via a domain-swapped arrangement. The trefoil-fold structure in isolation exposes considerable hydrophobic area that is otherwise buried in the intact β-trefoil trimeric assembly. The trefoil-fold sequence is not predicted to adopt the trefoil-fold architecture in ab initio folding studies; rather, the predicted fold is closely related to a compact “blade” motif from the β-propeller architecture. Expression of a trefoil-fold sequence and circular permutants shows that only the wild-type N-terminal motif definition yields an intact β-trefoil trimeric assembly, while permutants yield monomers. The results elucidate the folding requirements of the primordial trefoil-fold motif, and also suggest that this motif may sample a compact conformation that limits hydrophobic residue exposure, contains key trefoil-fold structural features, but is more structurally homologous to a β-propeller blade motif.
Identifier: FSU_libsubv1_scholarship_submission_1583283654_54e07068 (IID), 10.1002/pro.3850 (DOI)
Keywords: Protein evolution, folding pathway, domain-swapping, protein symmetry
Publication Note: This is the accepted manuscript, and the version of record can be found at https://doi.org/10.1002/pro.3850.
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1583283654_54e07068
Host Institution: FSU
Is Part Of: Protein Science.

Choose the citation style.
Tenorio, C., Longo, L., Parker, J., Lee, J., & Blaber, M. (2020). Ab initio Folding of a Trefoil-fold Motif Reveals Structural similarity with a β-propeller Blade Motif. Protein Science. Retrieved from http://purl.flvc.org/fsu/fd/FSU_libsubv1_scholarship_submission_1583283654_54e07068