Analysis of HIF-prolyl hydroxylases binding to substrates
Analysis of HIF-prolyl hydroxylases binding to substrates
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DOI：
10.1016/j.bbrc.2006.09.170
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发表时间：
2006-12-15
影响因子：
3.1
通讯作者：
del Peso, Luis
中科院分区：
文献类型：
--
作者：
Landazuri, Manuel O.;Vara-Vega, Alicia;del Peso, Luis
低氧诱导转录因子（HIF）主要受一组脯氨酸羟化酶（EGLN）调节，在氧存在下，EGLN靶向HIF进行降解。HIF α含有两个独立的氧降解结构域（N-ODD和C-ODD），它们是这些酶的底物。在这项工作中，我们采用酵母双杂交试验，以研究所需的序列决定簇的结合EGLN 1和3 HIF 1 α在细胞的情况下。我们的研究结果表明，虽然EGLN 1能够识别全长HIF 1 α蛋白中的两种ODD，但EGLN 3仅与CODD结合。内的残基取代的分析发现新的关键决定因素EGLN 1和3的结合。此外，我们的研究结果表明，这两种酶有一个非常相似的，虽然不相同，在其底物序列的特定位置的残基偏好。(c)2006年爱思唯尔公司All rights reserved.
Hypoxia inducible transcription factors (HIF) are mainly regulated by a group of proline hydroxylases (EGLNs) that, in the presence of oxygen, target HIF for degradation. HIF alpha contains two independent oxygen degradation domains (N-ODD and C-ODD) that are substrates for these enzymes. In this work, we employed the yeast two-hybrid assay to study the sequence determinants required for the binding of EGLN1 and 3 to HIF1 alpha in a cellular context. Our results demonstrate that, while EGLN1 is able to recognize both ODDs within full length HIF1 alpha protein, EGLN3 only binds to CODD. The analysis of the residue substitutions within CODD uncovered novel critical determinants for EGLN1 and 3 binding. In addition, our results show that both enzymes have a very similar, albeit not identical, residue preference at specific positions in their substrate sequences. (c) 2006 Elsevier Inc. All rights reserved.