title: Prevention and promotion effects of apolipoprotein E4 on amylin aggregation.
abstract: The misfolding of islet amyloid polypeptide (IAPP, amylin) results in the formation of islet amyloid, which is one of the most common pathological features of type 2 diabetes (T2D). Amylin, a 37-amino-acid peptide co-secreted with insulin and apolipoprotein E (ApoE) from the beta-cells of pancreatic islets, is thought to be responsible for the reduced mass of insulin-producing beta-cells. However, neither the relationship between amylin and ApoE nor the biological consequence of amylin misfolding is known. Here we have characterized the interaction between ApoE4 and amylin in vitro. We found that ApoE4 can strongly bind to amylin, and insulin can hardly inhibit amylin-ApoE binding. We further found that amylin fibrillization can be prevented by low concentration of ApoE4 and promoted by high concentration of ApoE4. Taken together, we propose that under physiological conditions ApoE4 efficiently binds and sequesters amylin, preventing its aggregation, and in T2D the enhanced ApoE4-amylin binding leads to the critical accumulation of amylin, facilitating islet amyloid formation.
authors.affiliation: Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Lei
authors.forename: Wei-hui
authors.initials: WH
authors.lastname: Wu
authors.forename: Ren-wang
authors.initials: RW
authors.lastname: Li
authors.forename: Jing-wen
authors.initials: JW
authors.lastname: Ma
authors.forename: Ye-ping
authors.initials: YP
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.forename: Yu-fen
authors.initials: YF
authors.lastname: Zhao
authors.forename: Yan-mei
authors.initials: YM
authors.lastname: Li
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000648:ultrastructure*; D053327:Apolipoprotein E4 / Q000737:chemistry* / Q000648:ultrastructure*; D001665:Binding Sites; D019281:Dimerization; D058228:Islet Amyloid Polypeptide; D046912:Multiprotein Complexes / Q000737:chemistry / Q000648:ultrastructure; D011485:Protein Binding
chemical_list: D000682:Amyloid; D053327:Apolipoprotein E4; D058228:Islet Amyloid Polypeptide; D046912:Multiprotein Complexes