Crystal structure and interactions of the PAS repeat region of the Drosophila clock protein PERIOD

Mol Cell. 2005 Jan 7;17(1):69-82. doi: 10.1016/j.molcel.2004.11.022.

Abstract

PERIOD proteins are central components of the Drosophila and mammalian circadian clock. Their function is controlled by daily changes in synthesis, cellular localization, phosphorylation, degradation, as well as specific interactions with other clock components. Here we present the crystal structure of a Drosophila PERIOD (dPER) fragment comprising two tandemly organized PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B) and two additional C-terminal alpha helices (alphaE and alphaF). Our analysis reveals a noncrystallographic dPER dimer mediated by intermolecular interactions of PAS-A with PAS-B and helix alphaF. We show that alphaF is essential for dPER homodimerization and that the PAS-A-alphaF interaction plays a crucial role in dPER clock function, as it is affected by the 29 hr long-period perL mutation.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Circadian Rhythm
  • Crystallography, X-Ray
  • Dimerization
  • Drosophila / chemistry
  • Drosophila / genetics
  • Drosophila / physiology
  • Drosophila Proteins / chemistry*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology
  • Period Circadian Proteins
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Repetitive Sequences, Amino Acid
  • Sequence Homology, Amino Acid
  • Static Electricity

Substances

  • Drosophila Proteins
  • Nuclear Proteins
  • PER protein, Drosophila
  • Period Circadian Proteins

Associated data

  • PDB/1WA9