title: Accommodation of a highly symmetric core within a symmetric protein superfold.
abstract: An alternative core packing group, involving a set of five positions, has been introduced into human acidic FGF-1. This alternative group was designed so as to constrain the primary structure within the core region to the same threefold symmetry present in the tertiary structure of the protein fold (the beta-trefoil superfold). The alternative core is essentially indistinguishable from the WT core with regard to structure, stability, and folding kinetics. The results show that the beta-trefoil superfold is compatible with a threefold symmetric constraint on the core region, as might be the case if the superfold arose as a result of gene duplication/fusion events. Furthermore, this new core arrangement can form the basis of a structural "building block" that can greatly simplify the de novo design of beta-trefoil proteins by using symmetric structural complementarity. Remaining asymmetry within the core appears to be related to asymmetry in the tertiary structure associated with receptor and heparin binding functionality of the growth factor.
authors: Kasha Laboratory, Institute of Molecular Biophysics and Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4380, USA.
authors: Stephen R
authors: SR
authors: Brych
authors: Jaewon
authors: J
authors: Kim
authors: Timothy M
authors: TM
authors: Logan
authors: Michael
authors: M
authors: Blaber
mesh_terms: D000595:Amino Acid Sequence; D002152:Calorimetry, Differential Scanning; D018360:Crystallography, X-Ray; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D013816:Thermodynamics
chemical_list: D016220:Fibroblast Growth Factor 1