Insulin fibril nucleation: The role of prefibrillar aggregates

被引:14
作者
Smith, M. I. [1 ,2 ]
Sharp, J. S. [1 ,2 ]
Roberts, C. J. [2 ,3 ]
机构
[1] Univ Nottingham, Sch Phys & Astron, Nottingham NG7 2RD, England
[2] Univ Nottingham, Nottingham Nanotechnol & Nanosci Ctr, Nottingham NG7 2RD, England
[3] Univ Nottingham, Sch Pharm, Lab Biophys & Surface Anal, Nottingham NG7 2RD, England
基金
英国工程与自然科学研究理事会;
关键词
D O I
10.1529/biophysj.108.131482
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
Dynamic light scattering and Fourier transform infrared spectroscopy were used to study the formation of prefibrillar aggregates and fibrils of bovine pancreatic insulin at 60 degrees C and at pH 1. The kinetics of disintegration of the prefibrillar aggregates were also studied using these techniques after a quench to 25 degrees C. These experiments reveal that formation of prefibrillar aggregates is reversible under the solution conditions studied and show that it is possible to significantly reduce the nucleation (lag) times associated with the onset of fibril growth in bovine pancreatic insulin solutions by increasing the concentration of prefibrillar aggregates in solution. These results provide convincing evidence that less structured prefibrillar aggregates can act as. bril-forming intermediates.
引用
收藏
页码:3400 / 3406
页数:7
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