期刊
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS
卷 11, 期 2, 页码 81-89出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/13506120412331272287
关键词
amyloid formation; aortic medial amyloid; protein misfolding; self-assembly; stacking interactions
Medin is the main constituent of aortic medial amyloid that occurs in virtually all individuals older than sixty. It is derived from a proteolytic fragment of lactadherin, a mammary epithelial cell expressed glycoprotein that is secreted as part of the milk fat globule membrane. It was previously demonstrated that an octapeptide fragment of medin (NH2-NFGSVQFV-COOH) forms typical well-ordered amyloid fibrils. To obtain further insights into the molecular determinants that mediate this process by such a short peptide fragment, we examined the amyloidogenic potential of its truncated forms and analogues. Our results clearly indicated that a truncated fragment of medin, the hexapeptide, NFGSVQ can form typical amyloid fibrils. A shorter pentapeptide fragment, NFGSV, self-assembled into a gel structure that exhibited a network of fibrous structures. The amyloid forming NFGSVQ hexapeptide is noticeably similar to the short amyloidogenic peptide fragments of the islet amyloid polypeptide (IAPP), NFGAIL and NFLVH Moreover, the substitution of the phenylalanine residue with either alanine or isoleucine significantly reduced the amyloidogenic potential of the peptide fragment. Taken together, the results are consistent with the assumed role of stacking interactions in the self-assembly processes that lead to the formation of amyloid fibrils. The results are discussed in the context of models for the mechanism of fibril formation and ways to design inhibitors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据