Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Biochem Biophys Res Commun. 2010 Dec 17;403(3-4):462-7. doi: 10.1016/j.bbrc.2010.11.058. Epub 2010 Nov 19.
Evidence has emerged that proinsulin C-peptide has at least three types of functional interactions in addition to its role during synthesis and secretion of insulin. Thus, C-peptide has been shown (i) to bind to cell membranes triggering G-protein-mediated intracellular signaling; (ii) to be internalized into cells and nuclei promoting transcription of rRNA and expression of particular genes; and (iii) to interact with peptides, including insulin, causing desaggregation of insulin oligomers like a chaperone, and with itself, causing homo-oligomers potentially capable of forming aggregates and deposits. In this work, we studied the insulin-C-peptide interactions by monitoring desaggregation and binding effects of C-peptide fragments on insulin. We find that the N-terminal segment of C-peptide harbors an interaction with insulin and that Glu11 appears to play a role in this action. We conclude that C-peptide fragments with this residue can mimic C-peptide in biophysical interactions with insulin, and that the insulin-interacting and membrane-interacting effects of C-peptide are distinct, ascribable to separate C-peptide segments, N- and C-terminally, respectively. The findings may have relevance to peptide effects in diabetic and healthy states.
有证据表明，胰岛素原 C 肽除了在胰岛素合成和分泌过程中发挥作用外，至少还有三种功能相互作用。因此，已经表明 C 肽 (i) 可以与细胞膜结合，触发 G 蛋白介导的细胞内信号转导；(ii) 被内吞到细胞和核内，促进 rRNA 的转录和特定基因的表达；(iii) 与包括胰岛素在内的肽相互作用，像伴侣一样使胰岛素寡聚物解聚，并与自身相互作用，可能形成具有聚集和沉积潜力的同型寡聚物。在这项工作中，我们通过监测 C 肽片段对胰岛素的解聚和结合作用来研究胰岛素-C 肽相互作用。我们发现 C 肽的 N 端片段与胰岛素具有相互作用，Glu11 似乎在这一作用中发挥作用。我们的结论是，具有该残基的 C 肽片段可以模拟 C 肽与胰岛素的生物物理相互作用，并且 C 肽的胰岛素相互作用和膜相互作用效应是不同的，可归因于分别位于 C 肽的 N 端和 C 端的不同 C 肽片段。这些发现可能与糖尿病和健康状态下的肽效应有关。
