Lipid Membranes Modulate the Structure of Islet Amyloid Polypeptide
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- 作者：Sajith A. Jayasinghe and Ralf Langen
- 刊名：Biochemistry
- 出版年：2005
- 出版时间：September 13, 2005
- 年：2005
- 卷：44
- 期：36
- 页码：12113 - 12119
- 全文大小：187K
- 年卷期：v.44,no.36(September 13, 2005)
- ISSN：1520-4995
文摘
The 37-residue islet amyloid polypeptide (IAPP) is thought to play an important role in thepathogenesis of type II diabetes. Despite a growing body of evidence implicating membrane interactionin IAPP toxicity, the membrane-bound form has not yet been well characterized. Here we used circulardichroism (CD) and fluorescence spectroscopy to investigate the molecular details of the interaction ofIAPP with lipid membranes of varying composition. In the presence of membranes containing negativelycharged phosphatidylserine (PS), we observed significant acceleration in the formation of IAPP aggregates.This acceleration is strongly modulated by the PS concentration and ionic strength, and is also observedat physiologically relevant PS concentrations. CD spectra of IAPP obtained immediately after the additionof membranes containing PS revealed features characteristic of an 
chars/alpha.gif" BORDER=0>-helical conformation approximately~15-19 residues in length. After a longer incubation with membranes, IAPP gave rise to CD spectracharacteristic of a chars/beta2.gif" BORDER=0 ALIGN="middle">-sheet conformation. Taken together, our CD and fluorescence data indicate thatconditions that promote weakly stable chars/alpha.gif" BORDER=0>-helical conformations may promote IAPP aggregation. Thepotential roles of IAPP-membrane interaction and the novel membrane-bound chars/alpha.gif" BORDER=0>-helical conformation inIAPP aggregation are discussed.
chars/alpha.gif" BORDER=0>-helical conformation approximately~15-19 residues in length. After a longer incubation with membranes, IAPP gave rise to CD spectracharacteristic of a chars/beta2.gif" BORDER=0 ALIGN="middle">-sheet conformation. Taken together, our CD and fluorescence data indicate thatconditions that promote weakly stable chars/alpha.gif" BORDER=0>-helical conformations may promote IAPP aggregation. Thepotential roles of IAPP-membrane interaction and the novel membrane-bound chars/alpha.gif" BORDER=0>-helical conformation inIAPP aggregation are discussed.