Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Unwinding the differences of the mammalian PERIOD clock proteins from crystal structure to cellular function

Nicole Kucera, Ira Schmalen, Sven Hennig, Rupert Öllinger, Holger M. Strauss, Astrid Grudziecki, Caroline Wieczorek, Achim Kramer and Eva Wolf
Proceedings of the National Academy of Sciences of the United States of America
Vol. 109, No. 9 (February 28, 2012), pp. 3311-3316
Stable URL: http://www.jstor.org/stable/41506947
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Unwinding the differences of the mammalian PERIOD clock proteins from crystal structure to cellular function
Preview not available

Abstract

The three PERIOD homologues mPER1, mPER2, and mPER3 constitute central components of the mammalian circadian clock. They contain two PAS (PER-ARNT-SIM) domains (PAS-A and PAS-B), which mediate homo-and heterodimeric mPER-mPER interactions as well as interactions with transcription factors and kinases. Here we present crystal structures of PAS domain fragments of mPER1 and mPER3 and compare them with the previously reported mPER2 structure. The structures reveal homodimers, which are mediated by interactions of the PAS-B β-sheet surface including a highly conserved tryptophan (Trp448mPER1, Trp419mPER2, Trp359mPER3). mPER1 homodimers are additionally stabilized by interactions between the PAS-A domains and mPER3 homodimers by an N-terminal region including a predicted helix-loop-helix motive. We have verified the existence of these homodimer interfaces in solution and inside cells using analytical gel filtration and luciferase complementation assays and quantified their contributions to homodimer stability by analytical ultracentrifugation. We also show by fluorescence recovery after photobleaching analyses that destabilization of the PAS-B/tryptophan dimer interface leads to a faster mobility of mPER2 containing complexes in human U2OS cells. Our study reveals structural and quantitative differences between the homodimeric interactions of the three mouse PERIOD homologues, which are likely to contribute to their distinct clock functions.

Page Thumbnails

  • Thumbnail: Page 
[3311]
    [3311]
  • Thumbnail: Page 
3312
    3312
  • Thumbnail: Page 
3313
    3313
  • Thumbnail: Page 
3314
    3314
  • Thumbnail: Page 
3315
    3315
  • Thumbnail: Page 
3316
    3316