An atomic resolution structure for human fibroblast growth factor 1
An atomic resolution structure for human fibroblast growth factor 1
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DOI：
10.1002/prot.20239
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发表时间：
2004-11-15
影响因子：
2.9
通讯作者：
Blaber, M
中科院分区：
文献类型：
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作者：
Bernett, MJ;Somasundaram, T;Blaber, M
人成纤维细胞生长因子 1 (FGF-1)（β-三叶超折叠的成员）的 1.10 埃原子分辨率 X 射线结构已被确定。 β-三叶形是 10 个基本蛋白质超折叠之一，也是唯一表现出三重结构对称性的超折叠（包含 3 个“三叶形”单元）。衍射数据的质量允许 Asn、Gln 和 His 旋转异构体、Pro 环褶皱的明确分配，以及原子各向异性位移参数 (ADP) 的细化。 FGF-1 结构表现出许多堆芯缺陷，可使用 1.0 埃探针半径进行检测。除了导致 FGF-1 的热稳定性相对较低之外，这些缺陷还可能允许结构内发生畴运动。精炼 ADP 的可用性允许对假定的刚体域进行平移/平移/螺旋 (TLS) 分析。 TLS分析表明，β链6-12一起形成刚体，并且相邻的羧基端和氨基端之间的TLS运动有清晰的分界。尽管与 β 链 6-12 分开，但各个 β 链 1-5 并不表现出相关运动；因此，该地区显得相对灵活。 FGF-1 的肝素结合触点位于 β 链 6-12 内；相反，受体结合触点的很大一部分位于 β 链 1-5 内。因此，在 FGF-1 中观察到的刚体运动似乎与配体结合功能相关。 (C) 2004 Wiley-Liss, Inc.
A 1.10-Angstrom 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-Angstrom 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. (C) 2004 Wiley-Liss, Inc.