Cryo-EM structures of human γ-secretase

Curr Opin Struct Biol. 2017 Oct;46:55-64. doi: 10.1016/j.sbi.2017.05.013. Epub 2017 Jul 17.

Abstract

γ-secretase, a membrane-embedded aspartate protease, catalyzes peptide bond hydrolysis of a large variety of type I integral membrane proteins exemplified by amyloid precursor protein (APP). Cleavage of APP leads to formation of β-amyloid plaque, which is a hallmark of Alzheimer's disease (AD). Over 200 AD-associated mutations are mapped to presenilin 1 (PS1), the catalytic component of γ-secretase. In the past three years, several cryo-electron microscopy (cryo-EM) structures of human γ-secretase have been determined at near atomic resolutions. Here we summarize the methods involved and discuss structural features of γ-secretase and the associated functional insights.

Publication types

  • Review

MeSH terms

  • Amyloid Precursor Protein Secretases / chemistry*
  • Amyloid Precursor Protein Secretases / genetics
  • Amyloid Precursor Protein Secretases / metabolism
  • Animals
  • Cryoelectron Microscopy / methods*
  • Gene Expression Regulation, Enzymologic
  • Humans

Substances

  • Amyloid Precursor Protein Secretases