Molecular insight of DREAM and presenilin 1 C-terminal fragment interactions

FEBS Lett. 2016 Apr;590(8):1114-22. doi: 10.1002/1873-3468.12156. Epub 2016 Apr 8.

Abstract

Interactions between downstream regulatory element antagonist modulator (DREAM) and presenilin 1 (PS1) are related to numerous neuronal processes. We demonstrate that association of PS1 carboxyl peptide (residues 445-467, HL9) with DREAM is calcium dependent and stabilized by a cluster of three aromatic residues: F462 and F465 from PS1 and F252 from DREAM. Additional stabilization is provided by residues in a loop connecting α helices 7 and 8 in DREAM and residues of PS1, namely cation-π interactions between R200 in DREAM and F465 in PS1 and the salt bridges formed by R207 in DREAM and D450 and D458 in PS1.

Keywords: Alzheimer's disease; DREAM; calsenilin; fluorescence anisotropy; potassium channel interacting protein; presenilin-binding interfaces.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Anisotropy
  • Calcium / metabolism
  • EF Hand Motifs
  • Humans
  • Kinetics
  • Kv Channel-Interacting Proteins / chemistry
  • Kv Channel-Interacting Proteins / metabolism*
  • Mice
  • Peptides / chemistry
  • Peptides / metabolism
  • Presenilin-1 / chemistry
  • Presenilin-1 / metabolism*
  • Protein Binding
  • Protein Domains
  • Protein Multimerization
  • Protein Structure, Secondary
  • Titrimetry

Substances

  • Amino Acids
  • Kv Channel-Interacting Proteins
  • Peptides
  • Presenilin-1
  • Calcium