The structure, molecular interactions and bioactivities of proinsulin C-peptide correlate with a tripartite molecule.
The structure, molecular interactions and bioactivities of proinsulin C-peptide correlate with a tripartite molecule.
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DOI：
10.1515/bmc-2014-0005
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发表时间：
2014-05-01
影响因子：
--
通讯作者：
Jornvall, Hans
中科院分区：
文献类型：
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作者：
Landreh, Michael;Johansson, Jan;Jornvall, Hans
多年来，许多生物学作用已被分配给胰岛素原C肽。有些似乎令人惊讶地完全不同，有时甚至是矛盾的，如监护人般的行动和储蓄倾向。这篇综述总结了最近报道的肽的生物分子相互作用，并介绍了它们如何与结构和功能方面到分区的分子结构。在结构水平上，C肽序列和折叠可以细分为三个不同的部分（“三重”）。在功能水平上，它的伴侣样能力，自组装，膜相互作用，以及与相关蛋白质的相互作用可以分别归因于这三个部分。在生物学水平上，分配是兼容的建议作用的C-肽在颗粒胰岛素储存，伴侣样活性的胰岛素低聚物，可能的存款倾向，并提出受体相互作用。最后，分配给进一步的生物活性肽，包括胰高血糖素和神经降压素有趣的相似之处。如果药物和临床试验成功完成，本解释应提供C肽作为健康和糖尿病重要的生物活性化合物的机制解释。
Many biological roles have been assigned to proinsulin C-peptide over the years. Some appear surprisingly disparate and sometimes even contradictory, like chaperone-like actions and depository tendencies. This review summarizes recently reported biomolecular interactions of the peptide and presents how they correlate with structural and functional aspects into a partitioned molecular architecture. At the structural level, the C-peptide sequence and fold can be subdivided into three distinct parts ('tripartite'). At the functional level, its chaperone-like abilities, self-assembly, and membrane interactions, as well as interactions with relevant proteins can be separately ascribed to these three segments. At the biological level, the assignments are compatible with the suggested roles of C-peptide in granular insulin storage, chaperone-like activities on insulin oligomers, possible depository tendencies, and proposed receptor interactions. Finally, the assignments give interesting parallels to further bioactive peptides, including glucagon and neurotensin. Provided pharmaceutical and clinical trials are successfully completed, the present interpretations should supply mechanistic explanations on C-peptide as a bioactive compound of importance in health and diabetes.