Comparison of physiological functions of antagonistic insulin-like peptides, INS-23 and INS-18, in Caenorhabditis elegans
Comparison of physiological functions of antagonistic insulin-like peptides, INS-23 and INS-18, in Caenorhabditis elegans
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秀丽隐杆线虫拮抗类胰岛素肽INS-23和INS-18的生理功能比较
DOI：
10.1080/09168451.2017.1415749
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
T. Kawano
中科院分区：
文献类型：
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作者：
Y. Matsunaga;T. Matsukawa;T. Iwasaki;K. Nagata;T. Kawano
在线虫中，胰岛素样肽通过胰岛素/IGF-1信号(IIS)途径在调节幼虫滞育和成虫寿命方面发挥重要作用。尽管已鉴定出40个胰岛素样多肽(ILPS)，但ILPS如何作为其唯一受体DAF-2的激动剂或拮抗剂仍不清楚。我们发现：1)INS-23与DAF-2拮抗剂一样，通过IIS途径发挥拮抗ILP促进幼虫滞育的作用；2)INS-23和INS-18具有相似的生化功能。此外，我们的分子模拟表明，与DAF-2激动剂相比，INS-23和INS-18在B区具有特征性的插入，这对于识别胰岛素受体是至关重要的。INS-23和INS-18在B区的这些特征插入将调节它们与DAF-2受体的分子间相互作用，这可能导致这些分子作为拮抗配体。我们的研究为了解ILPS的功能和结构提供了新的视角。
InCaenorhabditis elgans, insulin-like peptides have significant roles in modulating larval diapause and adult lifespan via the insulin/IGF-1 signaling (IIS) pathway. Although 40 insulin-like peptides (ILPs) have been identified, it remains unknown how ILPs act as either agonists or antagonists for their sole receptor, DAF-2. Here we found 1) INS-23 functions as an antagonistic ILP to promote larval diapause through the IIS pathway like a DAF-2 antagonist, INS-18, 2) INS-23 and INS-18 have similar biochemical functions. In addition, our molecular modeling suggests that INS-23 and INS-18 have characteristic insertions in the B-domain, which are crucial for the recognition of the insulin receptor, when compared with DAF-2 agonists. These characteristic insertions in the B-domain of INS-23 and INS-18 would modulate their intermolecular interactions with the DAF-2 receptor, which may lead these molecules to act as antagonistic ligands. Our study provides new insight into the function and structure of ILPs.