THREADING ANALYSIS SUGGESTS THAT THE OBESE GENE-PRODUCT MAY BE A HELICAL CYTOKINE
THREADING ANALYSIS SUGGESTS THAT THE OBESE GENE-PRODUCT MAY BE A HELICAL CYTOKINE
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DOI：
10.1016/0014-5793(95)00977-h
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发表时间：
1995-10-02
期刊：
影响因子：
3.5
通讯作者：
BRYANT, SH
中科院分区：
文献类型：
--
作者：
MADEJ, T;BOGUSKI, MS;BRYANT, SH
ob基因编码一种蛋白质，该蛋白质以突变形式与小鼠的肥胖和II型糖尿病相关。然而，序列分析显示与其他蛋白质没有相似性，也没有关于可能功能的线索。尽管如此，ob与其他蛋白质在功能上或祖先上相关的可能性仍然存在，其序列是不同的，只有三维结构的比较才能检测到关系，为了探索这种可能性，我们对三维结构数据库进行了“线程”搜索，以确定ob蛋白是否可能采用与任何已知结构相似的折叠。该搜索揭示了ob序列在P < 0.05的显著性水平上与来自螺旋细胞因子家族的结构相容，所述螺旋细胞因子家族包括白介素-2和生长激素，基于这些结果的ob的结构模型在物理上和生物学上是合理的，并导致可检验的预测，包括ob可能通过与类似于细胞因子家族的受体结合来激活JAK-STAT通路的预测。
The ob gene encodes a protein that, in mutant form, is associated with obesity and type II diabetes in mice, Sequence analysis has revealed no similarities to other proteins, however, and no clues as to possible functions, The possibility nonetheless remains that ob is functionally or ancestrally related to other proteins, whose sequences are divergent to the point that only a comparison of three-dimensional structures might detect relationship, To explore this possibility, we conduct a 'threading' search of a 3-dimensional structure database, to determine whether the ob protein might adopt a fold similar to any known structure, This search reveals that the ob sequence is compatible, at a significance level of P < 0.05, with structures from the family of helical cytokines that includes interleukin-2 and growth hormone, A structural model of ob based upon these results is physically and biologically plausible and leads to testable predictions, including the prediction that ob may activate the JAK-STAT pathway, via binding to a receptor resembling those of the cytokine family.