Fibril structure of amyloid-β(1-42) by cryo-electron microscopy

被引：638

作者：

Gremer, Lothar ^{[1
,2
]}

Schoelzel, Daniel ^{[1
,2
]}

Schenk, Carla ^{[1
]}

Reinartz, Elke ^{[2
]}

Labahn, Joerg ^{[1
,2
,3
]}

Ravelli, Raimond B. G. ^{[4
]}

Tusche, Markus ^{[1
]}

Lopez-Iglesias, Carmen ^{[4
]}

Hoyer, Wolfgang ^{[1
,2
]}

Heise, Henrike ^{[1
,2
]}

Willbold, Dieter ^{[1
,2
]}

Schroeder, Gunnar F. ^{[1
,5
]}

机构：

[1] Forschungszentrum Julich, Inst Complex Syst, Struct Biochem ICS 6, D-52425 Julich, Germany

[2] Heinrich Heine Univ Dusseldorf, Inst Phys Biol, D-40225 Dusseldorf, Germany

[3] DESY, CSSB, D-22607 Hamburg, Germany

[4] Maastricht Univ, Maastricht Multimodal Mol Imaging Inst, Univ Singel 50, NL-6229 ER Maastricht, Netherlands

[5] Heinrich Heine Univ Dusseldorf, Phys Dept, D-40225 Dusseldorf, Germany

来源：

SCIENCE | 2017年 / 358卷 / 6359期

基金：

欧洲研究理事会;

关键词：

ATOMIC-RESOLUTION STRUCTURE; AMYLOID-BETA FIBRILS; ALZHEIMERS-DISEASE; POLYMORPHISM; DIMER;

D O I：

10.1126/science.aao2825

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：

Amyloids are implicated in neurodegenerative diseases. Fibrillar aggregates of the amyloid-beta protein (A beta) are the main component of the senile plaques found in brains of Alzheimer's disease patients. We present the structure of an A beta(1-42) fibril composed of two intertwined protofilaments determined by cryo-electron microscopy (cryo-EM) to 4.0-angstrom resolution, complemented by solid-state nuclear magnetic resonance experiments. The backbone of all 42 residues and nearly all side chains are well resolved in the EM density map, including the entire N terminus, which is part of the cross-beta structure resulting in an overall "LS"-shaped topology of individual subunits. The dimer interface protects the hydrophobic C termini from the solvent. The characteristic staggering of the nonplanar subunits results in markedly different fibril ends, termed "groove" and "ridge," leading to different binding pathways on both fibril ends, which has implications for fibril growth.

引用

页码：116 / +

页数：4

共 20 条

[1] Atomic Resolution Structure of Monomorphic Aβ42 Amyloid Fibrils [J].