Structural highlights
Function
[PER2_MOUSE] Component of the circadian clock mechanism which is essential for generating circadian rhythms. Negative element in the circadian transcriptional loop. Influences clock function by interacting with other circadian regulatory proteins and transporting them to the nucleus. Negatively regulates CLOCK|NPAS2-BMAL1|BMAL2-induced transactivation.[1] [2]
Publication Abstract from PubMed
The mammalian circadian clock is driven by a transcriptional-translational feedback loop, which produces robust 24-hr rhythms. Proper oscillation of the clock depends on the complex formation and periodic turnover of the Period and Cryptochrome proteins, which together inhibit their own transcriptional activator complex, CLOCK-BMAL1. We determined the crystal structure of the CRY-binding domain (CBD) of PER2 in complex with CRY2 at 2.8 A resolution. PER2-CBD adopts a highly extended conformation, embracing CRY2 with a sinuous binding mode. Its N-terminal end tucks into CRY adjacent to a large pocket critical for CLOCK-BMAL1 binding, while its C-terminal half flanks the CRY2 C-terminal helix and sterically hinders the recognition of CRY2 by the FBXL3 ubiquitin ligase. Unexpectedly, a strictly conserved intermolecular zinc finger, whose integrity is important for clock rhythmicity, further stabilizes the complex. Our structure-guided analyses show that these interspersed CRY-interacting regions represent multiple functional modules of PERs at the CRY-binding interface.DOI: http://dx.doi.org/10.7554/eLife.03674.001.
Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex.,Nangle SN, Rosensweig C, Koike N, Tei H, Takahashi JS, Green CB, Zheng N Elife. 2014 Aug 15;3:e03674. doi: 10.7554/eLife.03674. PMID:25127877[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kume K, Zylka MJ, Sriram S, Shearman LP, Weaver DR, Jin X, Maywood ES, Hastings MH, Reppert SM. mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999 Jul 23;98(2):193-205. PMID:10428031
- ↑ Zhao WN, Malinin N, Yang FC, Staknis D, Gekakis N, Maier B, Reischl S, Kramer A, Weitz CJ. CIPC is a mammalian circadian clock protein without invertebrate homologues. Nat Cell Biol. 2007 Mar;9(3):268-75. Epub 2007 Feb 18. PMID:17310242 doi:http://dx.doi.org/10.1038/ncb1539
- ↑ Nangle SN, Rosensweig C, Koike N, Tei H, Takahashi JS, Green CB, Zheng N. Molecular assembly of the period-cryptochrome circadian transcriptional repressor complex. Elife. 2014 Aug 15;3:e03674. doi: 10.7554/eLife.03674. PMID:25127877 doi:http://dx.doi.org/10.7554/eLife.03674
