Protein Sci. 2005 Feb;14(2):351-9. Epub 2005 Jan 04

[DOI Link]

Sequence swapping does not result in conformation swapping for the ß4/ß5 and ß8/ß9 ß-hairpin turns in human acidic fibroblast growth factor

Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida 32306-4380, USA

The ß-turn is the most common type of nonrepetitive structure in globular proteins, comprising ~25% of all residues; however, a detailed understanding of effects of specific residues upon ß-turn stability and conformation is lacking. Human acidic fibroblast growth factor (FGF-1) is a member of the ß-trefoil superfold and contains a total of five ß-hairpin structures (antiparallel ß-sheets connected by a reverse turn). ß-Turns related by the characteristic threefold structural symmetry of this superfold exhibit different primary structures, and in some cases, different secondary structures. As such, they represent a useful system with which to study the role that turn sequences play in determining structure, stability, and folding of the protein. Two turns related by the threefold structural symmetry, the ß4/ß5 and ß8/ß9 turns, were subjected to both sequence-swapping and poly-glycine substitution mutations, and the effects upon stability, folding, and structure were investigated. In the wild-type protein these turns are of identical length, but exhibit different conformations. These conformations were observed to be retained during sequence-swapping and glycine substitution mutagenesis. The results indicate that the ß-turn structure at these positions is not determined by the turn sequence. Structural analysis suggests that residues flanking the turn are a primary structural determinant of the conformation within the turn.

PMID: 15632285 [PubMed - in process]

This publication is one of the several that describes a structure solved either at the Kasha Laboratory, Institute of Molecular Biophysics or in collaboration with the Institute Faculty. The data used for this structure determination came in full or part from the Macromolecular X-Ray Crystallography Facility.