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Weighing in on a Timeless controversy.

Jason Perry1

  • 1Division of Biological Sciences, University of California at San Diego, La Jolla, California 92093, USA. jmperry@biomail.ucsd.edu

Proteins
|October 19, 2005
PubMed
Summary

The Timeless protein in Drosophila is structurally composed of repetitive elements, including two ARM repeat domains. This finding clarifies its role in the circadian rhythm network and suggests functional similarities to other nuclear transport proteins.

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Area of Science:

  • Molecular Biology
  • Structural Biology
  • Chronobiology

Background:

  • Timeless (Tim) and Period (Per) proteins form heterodimers crucial for Drosophila's circadian rhythm.
  • Previous structural predictions for Tim using 3D-PSSM were debated.
  • Understanding Tim's structure is key to elucidating circadian gene regulation.

Purpose of the Study:

  • To resolve the structural nature of the Drosophila Timeless (Tim) protein.
  • To identify and characterize the repetitive structural elements within Tim.
  • To validate and refine previous computational structural predictions.

Main Methods:

  • A computer-assisted, manual approach was employed for structural analysis.
  • Identification and assignment of individual ARM structural units.
  • Phylogenetic analysis of ARM repeat relatedness.
  • Investigation of C-terminal domains.

Main Results:

  • Tim is confirmed to possess repetitive structural elements, including two ARM repeat domains.
  • Eleven individual ARM structural units were identified and their phylogenetic relationships analyzed.
  • A novel C-terminal prenyltransferase-like repeat domain was discovered in Tim.
  • Tim is classified as a member of the helical repeat protein superfamily.

Conclusions:

  • The study clarifies the structural composition of Tim, validating core aspects of prior predictions.
  • Tim's structure suggests functional analogies with karyopherin-like molecules involved in nuclear transport.
  • Further structural elucidation of Tim will enhance understanding of circadian clock mechanisms.

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