Presenilin adopts the ClC channel fold

Protein Sci. 2016 Jul;25(7):1363-5. doi: 10.1002/pro.2919. Epub 2016 Mar 23.


Presenilin is an integral membrane aspartate protease that regulates cellular processes by cleaving proteins within the cell membrane. The recent crystal structure of presenilin reveals a conspicuous pore in a bundle of nine α-helices, which was originally thought to adopt a novel protein fold. However, here I show that the presenilin fold is a variant of the ClC chloride channel/transporter fold. This observation may have important implications for presenilin's postulated biological role as a calcium leak channel.

Keywords: ClC channel; calcium leak channel; presenilin; protein fold.

MeSH terms

  • Animals
  • Chloride Channels / chemistry*
  • Crystallography, X-Ray
  • Models, Molecular
  • Presenilins / chemistry*
  • Protein Folding
  • Protein Structure, Secondary
  • Structure-Activity Relationship


  • Chloride Channels
  • Presenilins

Associated data

  • PDB/1OTS
  • PDB/4HYG