An atomic resolution structure for human fibroblast growth factor 1

A 1.10‐Å atomic resolution X‐ray structure of human fibroblast growth factor 1 (FGF‐1), a member of the β‐trefoil superfold, has been determined. The β‐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‐Å 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 β‐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 β‐strands 6–12, the individual β‐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 β‐strands 6–12; conversely, a significant portion of the receptor‐binding contacts are located within β‐strands 1–5. Thus, the observed rigid body motion in FGF‐1 appears related to the ligand‐binding functionalities. Proteins 2004. © 2004 Wiley‐Liss, Inc.