An atomic resolution structure for human fibroblast growth factor 1.
A 1.10-A atomic resolution X-ray structure of human fibroblast growth factor 1 (FGF-1), a member of the beta-trefoil superfold, has been determined. The beta-trefoil is one of 10 fundamental protein superfolds and is the only superfold to exhibit 3-fold structural symmetry (comprising 3 "trefoil" units). The quality of the diffraction data permits unambiguous assignment of Asn, Gln, and His rotamers, Pro ring pucker, as well as refinement of atomic anisotropic displacement parameters (ADPs). The FGF-1 structure exhibits numerous core-packing defects, detectable using a 1.0-A probe radius. In addition to contributing to the relatively low thermal stability of FGF-1, these defects may also permit domain motions within the structure. The availability of refined ADPs allows a translation/libration/screw (TLS) analysis of putative rigid body domains. The TLS analysis shows that beta-strands 6-12 together form a rigid body, and there is a clear demarcation in TLS motions between the adjacent carboxyl- and amino-termini. Although separate from beta-strands 6-12, the individual beta-strands 1-5 do not exhibit correlated motions; thus, this region appears to be comparatively flexible. The heparin-binding contacts of FGF-1 are located within beta-strands 6-12; conversely, a significant portion of the receptor-binding contacts are located within beta-strands 1-5. Thus, the observed rigid body motion in FGF-1 appears related to the ligand-binding functionalities.
Bernett
Matthew J
MJ
Institute of Molecular Biophysics and Department of Chemistry and Biochemistry, Florida State University, Tallahassee, Florida 32306-4380, USA.
Somasundaram
Thayumanasamy
T
Blaber
Michael
M
D016880:Anisotropy; D018360:Crystallography, X-Ray; D016220:Fibroblast Growth Factor 1 / Q000737:chemistry* / Q000378:metabolism; D006493:Heparin / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D009038:Motion; D018583:Pliability; D017433:Protein Structure, Secondary; D017468:Receptors, Fibroblast Growth Factor / Q000737:chemistry / Q000378:metabolism; D012997:Solvents / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics
D008024:Ligands; D017468:Receptors, Fibroblast Growth Factor; D012997:Solvents; D016220:Fibroblast Growth Factor 1; D006493:Heparin