Secondary Structure and Interfacial Aggregation of Amyloid-(1-40) on Sodium Dodecyl Sulfate Micelles
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- 作者：Vijayaraghavan Rangachari ; Dana Kim Reed ; Brenda D. Moore ; and Terrone L. Rosenberry
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：July 18, 2006
- 年：2006
- 卷：45
- 期：28
- 页码：8639 - 8648
- 全文大小：4240K
- 年卷期：v.45,no.28(July 18, 2006)
- ISSN：1520-4995
文摘
Alzheimer's disease (AD) is characterized by the presence of large numbers of fibrillar amyloiddeposits in the form of senile plaques in the brain. The fibrils in senile plaques are composed of 40- and42-residue amyloid-
(A) peptides. Several lines of evidence indicate that fibrillar A and especiallysoluble A aggregates are important in the pathogenesis of AD, and many laboratories have investigatedsoluble A aggregates generated from monomeric A in vitro. Of these in vitro aggregates, the bestcharacterized are called protofibrils. They are composed of globules and short rods, show primarily-structure by circular dichroism (CD), enhance the fluorescence of bound thioflavin T, and readily seedthe growth of long fibrils. However, one difficulty in correlating soluble A aggregates formed in vitrowith those in vivo is the high probability that cellular interfaces affect the aggregation rates and even theaggregate structures. Reports that focus on the features of interfaces that are important in A aggregationhave found that amphiphilic interactions and micellar-like A structures may play a role. We previouslydescribed the formation of A(1-40) aggregates at polar-nonpolar interfaces, including those generatedat microdroplets formed in dilute hexafluoro-2-propanol (HFIP). Here we compared the A(1-40)aggregates produced on sodium dodecyl sulfate (SDS) micelles, which may be a better model of biologicalmembranes with phospholipids that have anionic headgroups. At both HFIP and SDS interfaces, changesin peptide secondary structure were observed by CD immediately when A(1-40) was introduced. WithHFIP, the change involved an increase in predominant -structure content and in fluorescence with thioflavinT, while with SDS, a partial 
-helical conformation was adopted that gave no fluorescence. However, inboth systems, initial amorphous clustered aggregates progressed to soluble fibers rich in -structure overa roughly 2 day period. Fiber formation was much faster than in the absence of an interface, presumablybecause of the close intermolecular proximity of peptides at the interfaces. While these fibers resembledprotofibrils, they failed to seed the aggregation of A(1-40) monomers effectively.
(A) peptides. Several lines of evidence indicate that fibrillar A and especiallysoluble A aggregates are important in the pathogenesis of AD, and many laboratories have investigatedsoluble A aggregates generated from monomeric A in vitro. Of these in vitro aggregates, the bestcharacterized are called protofibrils. They are composed of globules and short rods, show primarily-structure by circular dichroism (CD), enhance the fluorescence of bound thioflavin T, and readily seedthe growth of long fibrils. However, one difficulty in correlating soluble A aggregates formed in vitrowith those in vivo is the high probability that cellular interfaces affect the aggregation rates and even theaggregate structures. Reports that focus on the features of interfaces that are important in A aggregationhave found that amphiphilic interactions and micellar-like A structures may play a role. We previouslydescribed the formation of A(1-40) aggregates at polar-nonpolar interfaces, including those generatedat microdroplets formed in dilute hexafluoro-2-propanol (HFIP). Here we compared the A(1-40)aggregates produced on sodium dodecyl sulfate (SDS) micelles, which may be a better model of biologicalmembranes with phospholipids that have anionic headgroups. At both HFIP and SDS interfaces, changesin peptide secondary structure were observed by CD immediately when A(1-40) was introduced. WithHFIP, the change involved an increase in predominant -structure content and in fluorescence with thioflavinT, while with SDS, a partial -helical conformation was adopted that gave no fluorescence. However, inboth systems, initial amorphous clustered aggregates progressed to soluble fibers rich in -structure overa roughly 2 day period. Fiber formation was much faster than in the absence of an interface, presumablybecause of the close intermolecular proximity of peptides at the interfaces. While these fibers resembledprotofibrils, they failed to seed the aggregation of A(1-40) monomers effectively.