3-DIMENSIONAL STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH-FACTOR
3-DIMENSIONAL STRUCTURE OF HUMAN BASIC FIBROBLAST GROWTH-FACTOR
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DOI：
10.1073/pnas.88.8.3441
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发表时间：
1991-04-01
影响因子：
11.1
通讯作者：
MATTHEWS, BW
中科院分区：
文献类型：
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作者：
ERIKSSON, AE;COUSENS, LS;MATTHEWS, BW
用X射线结晶学测定了人碱性成纤维细胞生长因子的三维结构，在2.2埃分辨率下，其结晶残留量为17.4%。通过使用三个重原子导数的多重同象替换，以2.8埃的名义分辨率最初求解了该结构。虽然图谱清楚地显示了分子的整体折叠，但没有观察到前19个氨基末端和最后3个羧基末端氨基酸的电子密度，表明它们是无序的。在pH为8.1的P1空间群中，从2.0M硫酸铵溶液中生长出晶体，晶胞尺寸a=30.9埃，b=33.4埃，c=35.9埃，α=59.5度，β=72.0度，伽马=75.6度。每个单位细胞有一个分子，晶体的衍射率超过1.9埃。碱性成纤维细胞生长因子的整体结构可以描述为具有与已报道的白细胞介素1-β、白细胞介素1-α和大豆胰蛋白酶抑制物非常相似的折叠的三角金字塔。一个明显的硫酸盐离子结合在分子表面的碱性区域内，并以Arg-120的主链酰胺和Asn-27、Arg-120和Lys-125的侧链为配体。推测这是肝素的结合部位。残基106-115，被认为与bFGF受体结合[Baird，A.，Schubert，D.，Ling，N.&Guillmin，R.(1988)Proc.娜塔莉。阿卡德。SCI。USA85,2324-2328]包括一个从蛋白质表面延伸的不规则环，距离推测的肝素结合部位约25埃。这个假定的受体结合环的主干结构与白介素1-β的相应区域非常相似，尽管不完全相同。
The three-dimensional structure of human basic fibroblast growth factor (bFGF) has been determined by x-ray crystallography and refined to a crystallographic residual of 17.4% at 2.2-angstrom resolution. The structure was initially solved at a nominal resolution of 2.8 angstrom by multiple isomorphous replacement using three heavy-atom derivatives. Although the map clearly showed the overall fold of the molecule, electron density was not observed for the first 19 amino-terminal and the last 3 carboxyl-terminal amino acids, suggesting that they are disordered. The bFGF crystals were grown from 2.0 M ammonium sulfate at pH 8.1 in space group P1 with cel' dimensions a = 30.9 angstrom, b = 33.4 angstrom, c = 35.9 angstrom,alpha = 59.5-degrees, beta = 72.0-degrees, and gamma = 75.6-degrees. There is one molecule per unit cell and the crystals diffract to spacings beyond 1.9 angstrom. The overall structure of bFGF can be described as a trigonal pyramid with a fold very similar to that reported for interleukin 1-beta, interleukin 1-alpha, and soybean trypsin inhibitor. An apparent sulfate ion is bound within a basic region on the surface of the molecule and has as ligands the main-chain amide of Arg-120 and the side chains of Asn-27, Arg-120, and Lys-125. This is suggested as the presumed binding site for heparin. Residues 106-115, which are presumed to bind to the bFGF receptor [Baird, A., Schubert, D., Ling, N. & Guillemin, R. (1988) Proc. Natl. Acad. Sci. USA 85, 2324-2328], include an irregular loop that extends somewhat from the surface of the protein and is about 25 angstrom from the presumed heparin binding site. The backbone structure of this putative receptor-binding loop is very similar, although not identical, to the corresponding region of interleukin 1-beta.