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

Lothar Gremer, Daniel Schoelzel, Carla Schenk, Elke Reinartz, Joerg Labahn, Raimond B. G. Ravelli, Markus Tusche, Carmen Lopez-Iglesias, Wolfgang Hoyer, Henrike Heise, Dieter Willbold*, Gunnar F. Schröder*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)116-119
Number of pages4
JournalScience
Volume358
Issue number6359
DOIs
Publication statusPublished - 6 Oct 2017

Keywords

  • ATOMIC-RESOLUTION STRUCTURE
  • BETA-AMYLOID FIBRILS
  • ALZHEIMERS-DISEASE
  • CRYO-EM
  • POLYMORPHISM

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