Comparison of Alzheimer Aβ(1-40) and Aβ(1-42) amyloid fibrils reveals similar protofilament structures

被引：211

作者：

Schmidt, Matthias ^{[1
,2
,3
,4
]}

Sachse, Carsten ^{[1
,3
,4
]}

Richter, Walter ^{[5
]}

Xu, Chen ^{[1
]}

Faendrich, Marcus ^{[3
,4
]}

Grigorieff, Nikolaus ^{[1
,2
]}

机构：

[1] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Waltham, MA 02454 USA

[2] Brandeis Univ, Howard Hughes Med Inst, Waltham, MA 02454 USA

[3] Max Planck Res Unit Enzymol Prot Folding, D-01620 Halle, Saale, Germany

[4] Univ Halle Wittenberg, D-01620 Halle, Saale, Germany

[5] Univ Jena, Elektronenmikroskop Zentrum, D-07740 Jena, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 47期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; electron microscopy; prion; protein folding; A-BETA; ELECTRON-MICROSCOPY; EXPERIMENTAL CONSTRAINTS; QUATERNARY STRUCTURE; PROTEIN; POLYMORPHISM; PEPTIDE; MODEL;

D O I：

10.1073/pnas.0905007106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We performed mass-per-length (MPL) measurements and electron cryomicroscopy (cryo-EM) with 3D reconstruction on an A beta(1-42) amyloid fibril morphology formed under physiological pH conditions. The data show that the examined A beta(1-42) fibril morphology has only one protofilament, although two protofilaments were observed with a previously studied A beta(1-40) fibril. The latter fibril was resolved at 8 angstrom resolution showing pairs of beta-sheets at the cores of the two protofilaments making up a fibril. Detailed comparison of the A beta(1-42) and A beta(1-40) fibril structures reveals that they share an axial twofold symmetry and a similar protofilament structure. Furthermore, the MPL data indicate that the protofilaments of the examined A beta(1-40) and A beta(1-42) fibrils have the same number of A beta molecules per cross-beta repeat. Based on this data and the previously studied A beta(1-40) fibril structure, we describe a model for the arrangement of peptides within the A beta(1-42) fibril.

引用

页码：19813 / 19818

页数：6

共 38 条

[21] The solvent protection of Alzheimer amyloid-β-(1-42) fibrils as determined by solution NMR spectroscopy [J].

Olofsson, A ;

Sauer-Eriksson, AE ;

Öhman, A .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (01) :477-483

[22] Molecular structural basis for polymorphism in Alzheimer's β-amyloid fibrils [J].

Paravastu, Anant K. ;

Leapman, Richard D. ;

Yau, Wai-Ming ;

Tycko, Robert .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (47) :18349-18354

[23] Self-propagating, molecular-level polymorphism in Alzheimer's β-amyloid fibrils [J].

Petkova, AT ;

Leapman, RD ;

Guo, ZH ;

Yau, WM ;

Mattson, MP ;

Tycko, R .

SCIENCE, 2005, 307 (5707) :262-265

[24] A structural model for Alzheimer's β-amyloid fibrils based on experimental constraints from solid state NMR [J].

Petkova, AT ;

Ishii, Y ;

Balbach, JJ ;

Antzutkin, ON ;

Leapman, RD ;

Delaglio, F ;

Tycko, R .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (26) :16742-16747

[25] Experimental constraints on quaternary structure in Alzheimer's β-amyloid fibrils [J].

Petkova, AT ;

Yau, WM ;

Tycko, R .

BIOCHEMISTRY, 2006, 45 (02) :498-512

[26] Towards an understanding of the structural molecular mechanism of β2-microglobulin amyloid formation in vitro [J].

Radford, SE ;

Gosal, WS ;

Platt, GW .

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS, 2005, 1753 (01) :51-63

[27] Paired β-sheet structure of an Aβ(1-40) amyloid fibril revealed by electron microscopy [J].

Sachse, Carsten ;

Faendrich, Marcus ;

Grigorieff, Nikolaus .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (21) :7462-7466

[28] High-resolution electron microscopy of helical specimens:: A fresh look at Tobacco Mosaic Virus [J].

Sachse, Carsten ;

Chen, James Z. ;

Coureux, Pierre-Damien ;

Stroupe, M. Elizabeth ;

Faendrich, Marcus ;

Grigorieff, Nikolaus .

JOURNAL OF MOLECULAR BIOLOGY, 2007, 371 (03) :812-835

[29] Quaternary structure of a mature amyloid fibril from Alzheimer's aβ(1-40) peptide [J].

Sachse, Carsten ;

Xu, Chen ;

Wieligmann, Karin ;

Diekmann, Stephan ;

Grigorieff, Nikolaus ;

Faendrich, Marcus .

JOURNAL OF MOLECULAR BIOLOGY, 2006, 362 (02) :347-354

[30] Inhibitors of amyloid toxicity based on β-sheet packing of Aβ40 and Aβ42 [J].

Sato, T ;

Kienlen-Campard, P ;

Ahmed, M ;

Liu, W ;

Li, HL ;

Elliott, JI ;

Aimoto, S ;

Constantinescu, SN ;

Octave, JN ;

Smith, SO .

BIOCHEMISTRY, 2006, 45 (17) :5503-5516

← 1 2 3 4 →