Structural consideration of mammalian D-aspartyl endopeptidase

Chem Biodivers. 2010 Jun;7(6):1403-7. doi: 10.1002/cbdv.200900346.

Abstract

D-aspartyl endopeptidase (DAEP) is a specific protease for D-aspartic acid (D-Asp)-containing protein, which has been implicated in the pathogenesis of age-related and misfolding diseases such as Alzheimer's disease. Therefore, DAEP would serve as a defensive system against the noxious D-Asp-containing protein. However, it is unclear how DAEP exerts its unique enzymatic function, since its higher-order structure remains quite unsolved. In this study, we analyzed the conformation of purified DAEP from the mitochondrial membrane of mouse by atomic force microscopy the advantage of which is its ability to study biological macromolecules and even living organisms in an ambient air environment. DAEP formed a ring-like structure with a diameter of ca. 40 nm. Our data suggest that DAEP topologically belongs to the AAA+ protease family such as proteasome, Lon, and mitochondrial membrane-bound i-/m-AAA protease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Animals
  • Aspartic Acid Endopeptidases / chemistry*
  • Aspartic Acid Endopeptidases / metabolism
  • D-Aspartic Acid / metabolism
  • Mice
  • Microscopy, Atomic Force
  • Mitochondrial Membranes / enzymology

Substances

  • D-Aspartic Acid
  • Aspartic Acid Endopeptidases