title: A polypeptide "building block" for the β-trefoil fold identified by "top-down symmetric deconstruction".
abstract: Fibroblast growth factor-1, a member of the 3-fold symmetric β-trefoil fold, was subjected to a series of symmetric constraint mutations in a process termed "top-down symmetric deconstruction." The mutations enforced a cumulative exact 3-fold symmetry upon symmetrically equivalent positions within the protein and were combined with a stability screen. This process culminated in a β-trefoil protein with exact 3-fold primary-structure symmetry that exhibited excellent folding and stability properties. Subsequent fragmentation of the repeating primary-structure motif yielded a 42-residue polypeptide capable of spontaneous assembly as a homotrimer, producing a thermostable β-trefoil architecture. The results show that despite pronounced reduction in sequence complexity, pure symmetry in the design of a foldable, thermostable β-trefoil fold is possible. The top-down symmetric deconstruction approach provides a novel alternative means to successfully identify a useful polypeptide "building block" for subsequent "bottom-up" de novo design of target protein architecture.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306-4300, USA.
authors.forename: Jihun
authors.initials: J
authors.lastname: Lee
authors.forename: Sachiko I
authors.initials: SI
authors.lastname: Blaber
authors.forename: Vikash K
authors.initials: VK
authors.lastname: Dubey
authors.forename: Michael
authors.initials: M
authors.lastname: Blaber
mesh_terms: D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D018360:Crystallography, X-Ray; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry / Q000235:genetics; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000235:genetics; D011489:Protein Denaturation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D010455:Peptides; D016220:Fibroblast Growth Factor 1; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1