Identification of residues in human neuroglobin crucial for guanine nucleotide dissociation inhibitor activity
Identification of residues in human neuroglobin crucial for guanine nucleotide dissociation inhibitor activity
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DOI：
10.1021/bi0477539
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发表时间：
2005-03-01
期刊：
影响因子：
2.9
通讯作者：
Morishima, I
中科院分区：
文献类型：
--
作者：
Wakasugi, K;Morishima, I
神经球蛋白（Ngb）是最近发现的一种脊椎动物血红素蛋白，在大脑中表达，可以可逆地结合氧。我们之前证明，人三价铁 Ngb 与异三聚体 G 蛋白 (Galpha) 的 α 亚基结合，并充当 Galpha 的鸟嘌呤核苷酸解离抑制剂 (GDI)。在这里，我们更详细地研究了 Ngb 和 Galpha 之间的相互作用。我们报告说，斑马鱼 Ngb 与人类 Ngb 具有约 50% 的氨基酸序列同一性，但不具有 Galpha 的 GDI 活性。通过在斑马鱼和人类 Ngb 之间进行外显子交换和定点诱变，我们鉴定了几个对人类 Ngb 的 GDI 活性至关重要的残基。
Neuroglobin (Ngb) is a recently discovered vertebrate heme protein that is expressed in the brain and can reversibly bind oxygen. We previously demonstrated that ferric human Ngb binds to the alpha-subunits of heterotrimeric G proteins (Galpha) and acts as a guanine nucleotide dissociation inhibitor (GDI) for Galpha. Here we have investigated the interaction between Ngb and Galpha in more detail. We report that zebrafish Ngb, which shares about 50% amino acid sequence identity with human Ngb, does not have a GDI activity for Galpha. By carrying out exon swapping between zebrafish and human Ngb and site-directed mutagenesis, we have identified several residues that are crucial for the GDI activity of human Ngb.