Amyloid Formation in Heterogeneous Environments: Islet Amyloid Polypeptide Glycosaminoglycan Interactions

被引:28
作者
Wang, Hui [1 ]
Cao, Ping [1 ]
Raleigh, Daniel P. [1 ,2 ]
机构
[1] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA
[2] SUNY Stony Brook, Grad Program Biochem & Struct Biol, Grad Program Biophys, Stony Brook, NY 11794 USA
基金
美国国家卫生研究院;
关键词
IAPP; amylin; glycosaminoglycan; extracellular matrix; amyloid; FORMATION IN-VITRO; HEPARAN-SULFATE PROTEOGLYCANS; ALZHEIMERS-DISEASE; FIBRIL FORMATION; DIABETES-MELLITUS; BASEMENT-MEMBRANE; PROTEIN; INHIBITION; AMYLIN; IAPP;
D O I
10.1016/j.jmb.2012.11.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Amyloid formation plays an important role in a broad range of diseases, and the search for amyloid inhibitors is an active area of research. Amyloid formation takes places in a heterogeneous environment in vivo with the potential for interactions with membranes and with components of the extracellular matrix. Naturally occurring amyloid deposits are associated with sulfated proteoglycans and other factors. However, the vast majority of in vitro assays of amyloid formation and amyloid inhibition are conducted in homogeneous solution where the potential for interactions with membranes or sulfated proteoglycans is lacking and it is possible that different results may be obtained in heterogeneous environments. We show that variants of islet amyloid polypeptide (IAPP), which are non-amyloidogenic in homogeneous solution, can be readily induced to form amyloid in the presence of glycosaminoglycans (GAGs). GAGs are found to be more effective than anionic lipid vesicles at inducing amyloid formation on a per-charge basis. Several known inhibitors of IAPP amyloid formation are shown to be less effective in the presence of GAGs. (C) 2012 Published by Elsevier Ltd.
引用
收藏
页码:492 / 505
页数:14
相关论文
共 61 条
[1]   Recovery and purification of highly aggregation-prone disulfide-containing peptides: Application to islet amyloid polypeptide [J].
Abedini, A ;
Singh, G ;
Raleigh, DP .
ANALYTICAL BIOCHEMISTRY, 2006, 351 (02) :181-186
[2]   The role of His-18 in amyloid formation by human islet amyloid polypeptide [J].
Abedini, A ;
Raleigh, DP .
BIOCHEMISTRY, 2005, 44 (49) :16284-16291
[3]   Incorporation of pseudoproline derivatives allows the facile synthesis of human IAPP, a highly amyloidogenic and aggregation-prone polypeptide [J].
Abedini, A ;
Raleigh, DP .
ORGANIC LETTERS, 2005, 7 (04) :693-696
[4]   A single-point mutation converts the highly amyloidogenic human islet amyloid polypeptide into a potent fibrillization inhibitor [J].
Abedini, Andisheh ;
Meng, Fanling ;
Raleigh, Daniel P. .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2007, 129 (37) :11300-+
[5]   Characterization of the heparin binding site in the N-terminus of human pro-islet amyloid polypeptide: Implications for amyloid formation [J].
Abedini, Andisheh ;
Tracz, Sylvia M. ;
Cho, Jae-Hyun ;
Raleigh, Daniel P. .
BIOCHEMISTRY, 2006, 45 (30) :9228-9237
[6]   Amyloidogenesis: historical and modern observations point to heparan sulfate proteoglycans as a major culprit [J].
Ancsin, JB .
AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS, 2003, 10 (02) :67-79
[7]   Amyloid Deposition in Transplanted Human Pancreatic Islets: A Conceivable Cause of Their Long-Term Failure [J].
Andersson, Arne ;
Bohman, Sara ;
Borg, L. A. Hakan ;
Paulsson, Johan F. ;
Schultz, Sebastian W. ;
Westermark, Gunilla T. ;
Westermark, Per .
EXPERIMENTAL DIABETES RESEARCH, 2008, :562985
[8]   EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity [J].
Bieschke, Jan ;
Russ, Jenny ;
Friedrich, Ralf P. ;
Ehrnhoefer, Dagmar E. ;
Wobst, Heike ;
Neugebauer, Katja ;
Wanker, Erich E. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (17) :7710-7715
[9]   Small Molecule Protein-Protein Interaction Inhibitors as CNS Therapeutic Agents: Current Progress and Future Hurdles [J].
Blazer, Levi L. ;
Neubig, Richard R. .
NEUROPSYCHOPHARMACOLOGY, 2009, 34 (01) :126-141
[10]   'In vitro' amyloid fibril formation from transthyretin: The influence of ions and the amyloidogenicity of TTR variants [J].
Bonifacio, MJ ;
Sakaki, Y ;
Saraiva, MJ .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1996, 1316 (01) :35-42