Crystal structure of imaginal disc growth factor-2 -: A member of a new family of growth-promoting glycoproteins from Drosophila melanogaster
Crystal structure of imaginal disc growth factor-2 -: A member of a new family of growth-promoting glycoproteins from Drosophila melanogaster
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DOI：
10.1074/jbc.m110502200
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发表时间：
2002-04-12
影响因子：
4.8
通讯作者：
Tormo, J
中科院分区：
文献类型：
--
作者：
Varela, PF;Llera, AS;Tormo, J
想象盘生长因子-2 （IDGF-2）是最近发现的果蝇黑胃可溶性多肽生长因子家族的一员，可促进想象盘细胞增殖。虽然它们的确切作用方式尚未确定，但IDGFs与胰岛素合作刺激影像学椎间盘细胞的生长。我们报道了IDGF-2在1.3埃分辨率下的晶体结构。该结构为18家族糖基水解酶的经典（β - α）(8)桶状折叠，并插入α + β结构域，类似于粘质沙雷氏菌几丁质酶A和b。几丁质酶催化序列的氨基酸替换使得IDGF-2在其假定的配体结合位点具有较少的负电荷环境，并排除了几丁质水解的亲核攻击机制。特别重要的是，Glu在132位被Gln取代，这已被证明可以消除几丁质酶的酶活性。然而，参与寡糖识别的残基的适度保守表明，IDGF-2可以结合碳水化合物，假设几个构象改变来打开部分封闭的结合位点。因此，IDGFs可能从几丁质酶进化而来，获得了作为生长因子的新功能，与细胞表面糖蛋白相互作用，参与促进生长的过程，如果蝇胰岛素受体。
Imaginal disc growth factor-2 (IDGF-2) is a member of a recently described family of Drosophila melanogaster-soluble polypeptide growth factors that promote cell proliferation in imaginal discs. Although their precise mode of action has not been established, IDGFs cooperate with insulin in stimulating the growth of imaginal disc cells. We report the crystal structure of IDGF-2 at 1.3-Angstrom resolution. The structure shows the classical (betaalpha)(8) barrel-fold of family 18 glycosyl hydrolases, with an insertion of an alpha + beta domain similar to that of Serratia marcescens chitinases A and B. However, amino acid substitutions in the consensus catalytic sequence of chitinases give IDGF-2 a less negatively charged environment in its putative ligand-binding site and preclude the nucleophilic attack mechanism of chitin hydrolysis' Particularly important is the replacement of Glu by Gln at position 132, which has been shown to abolish enzymatic activity in chitinases. Nevertheless, a modest conservation of residues that participate in oligosaccharide recognition suggests that IDGF-2 could bind carbohydrates, assuming several conformational changes to open the partially occluded binding site. Thus, IDGFs may have evolved from chitinases to acquire new functions as growth factors, interacting with cell surface glycoproteins implicated in growth-promoting processes, such as the Drosophila insulin receptor.