Formation of Dynamic Soluble Surfactant-induced Amyloid β Peptide Aggregation Intermediates

被引:47
作者
Abelein, Axel [1 ]
Kaspersen, Jorn Dovling [2 ,3 ]
Nielsen, Soren Bang [4 ]
Jensen, Grethe Vestergaard [2 ,3 ]
Christiansen, Gunna [5 ]
Pedersen, Jan Skov [2 ,3 ]
Danielsson, Jens [1 ]
Otzen, Daniel E. [4 ]
Graslund, Astrid [1 ]
机构
[1] Stockholm Univ, Dept Biochem & Biophys, SE-10691 Stockholm, Sweden
[2] Aarhus Univ, Interdisciplinary Nanosci Ctr iNANO, DK-8000 Aarhus, Denmark
[3] Aarhus Univ, Dept Chem, DK-8000 Aarhus, Denmark
[4] Aarhus Univ, Ctr Insoluble Prot Struct InSPIN, DK-8000 Aarhus, Denmark
[5] Aarhus Univ, Dept Biomed Med Microbiol & Immunol, DK-8000 Aarhus, Denmark
基金
瑞典研究理事会;
关键词
SOLID-STATE NMR; ANGLE NEUTRON-SCATTERING; ALZHEIMERS-DISEASE; ALPHA-SYNUCLEIN; PROTEIN AGGREGATION; CONGO RED; FIBRILS; MICELLES; FIBRILLATION; PROBES;
D O I
10.1074/jbc.M113.470450
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
Intermediate amyloidogenic states along the amyloid beta peptide (A beta) aggregation pathway have been shown to be linked to neurotoxicity. To shed more light on the different structures that may arise during A beta aggregation, we here investigate surfactant-induced A beta aggregation. This process leads to co-aggregates featuring a beta-structure motif that is characteristic for mature amyloid-like structures. Surfactants induce secondary structure in A beta in a concentration-dependent manner, from predominantly random coil at low surfactant concentration, via beta-structure to the fully formed beta-helical state at high surfactant concentration. The beta-rich state is the most aggregation-prone as monitored by thioflavin T fluorescence. Small angle x-ray scattering reveals initial globular structures of surfactant-A beta co-aggregated oligomers and formation of elongated fibrils during a slow aggregation process. Alongside this slow (minutes to hours time scale) fibrillation process, much faster dynamic exchange (k(ex) similar to 1100 s(-1)) takes place between free and co-aggregate-bound peptide. The two hydrophobic segments of the peptide are directly involved in the chemical exchange and interact with the hydrophobic part of the co-aggregates. Our findings suggest a model for surfactant-induced aggregation where free peptide and surfactant initially co-aggregate to dynamic globular oligomers and eventually form elongated fibrils. When interacting with beta-structure promoting substances, such as surfactants, A beta is kinetically driven toward an aggregation-prone state.
引用
收藏
页码:23518 / 23528
页数:11
相关论文
共 65 条
[11]  
Cavanagh J, 2007, PROTEIN NMR SPECTROSCOPY: PRINCIPLES AND PRACTICE, 2ND EDITION, P333, DOI 10.1016/B978-012164491-8/50007-5
[12]   Evidence of fibril-like β-sheet structures in a neurotoxic amyloid intermediate of Alzheimer's β-amyloid [J].
Chimon, Sandra ;
Shaibat, Medhat A. ;
Jones, Christopher R. ;
Calero, Diana C. ;
Aizezi, Buzulagu ;
Ishii, Yoshitaka .
NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2007, 14 (12) :1157-1164
[13]   Protein misfolding, functional amyloid, and human disease [J].
Chiti, Fabrizio ;
Dobson, Christopher M. .
ANNUAL REVIEW OF BIOCHEMISTRY, 2006, 75 :333-366
[14]   From Macroscopic Measurements to Microscopic Mechanisms of Protein Aggregation [J].
Cohen, Samuel I. A. ;
Vendruscolo, Michele ;
Dobson, Christopher M. ;
Knowles, Tuomas P. J. .
JOURNAL OF MOLECULAR BIOLOGY, 2012, 421 (2-3) :160-171
[15]   The Alzheimer β-peptide shows temperature-dependent transitions between left-handed 31-helix, β-strand and random coil secondary structures [J].
Danielsson, J ;
Jarvet, J ;
Damberg, P ;
Gräslund, A .
FEBS JOURNAL, 2005, 272 (15) :3938-3949
[16]   15N relaxation study of the amyloid β-peptide:: structural propensities and persistence length [J].
Danielsson, Jens ;
Andersson, August ;
Jarvet, Juri ;
Graslund, Astrid .
MAGNETIC RESONANCE IN CHEMISTRY, 2006, 44 :S114-S121
[17]   DIRECT MEASUREMENTS OF THE DISSOCIATION-RATE CONSTANT FOR INHIBITOR-ENZYME COMPLEXES VIA THE T-1-RHO AND T-2 (CPMG) METHODS [J].
DAVIS, DG ;
PERLMAN, ME ;
LONDON, RE .
JOURNAL OF MAGNETIC RESONANCE SERIES B, 1994, 104 (03) :266-275
[18]   On the structural definition of amyloid fibrils and other polypeptide aggregates [J].
Faendrich, M. .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2007, 64 (16) :2066-2078
[19]   Oligomeric Intermediates in Amyloid Formation: Structure Determination and Mechanisms of Toxicity [J].
Faendrich, Marcus .
JOURNAL OF MOLECULAR BIOLOGY, 2012, 421 (4-5) :427-440
[20]   Recent progress in understanding Alzheimer's β-amyloid structures [J].
Faendrich, Marcus ;
Schmidt, Matthias ;
Grigorieff, Nikolaus .
TRENDS IN BIOCHEMICAL SCIENCES, 2011, 36 (06) :338-345