期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：29
页码：10584-10589
DOI：10.1073/pnas.0403756101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In humans suffering from dialysis-related amyloidosis, the protein {beta}2-microglobulin ({beta}2M) is deposited as an amyloid; however, an amyloid of {beta}2M is unknown in mice. {beta}2M sequences from human and mouse are 70% identical, but there is a seven-residue peptide in which six residues differ. This peptide from human {beta}2M forms amyloid in vitro, whereas the mouse peptide does not. Substitution of the human peptide for its counterpart in the mouse sequence results in the formation of amyloid in vitro. These results show that a seven-residue segment of human {beta}2M is sufficient to convert {beta}2M to the amyloid state, and that specific residue interactions are crucial to the conversion. These observations are consistent with a proposed Zipper-spine model for {beta}2M amyloid, in which the spine of the fibril consists of an anhydrous {beta}-sheet.
