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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)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Washington, Seattle, United States.

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Related in: MedlinePlus

CRY-PHR superposition: including CRY1 apo (red), CRY2 apo (light blue), KL001-bound (green), FAD-bound (orange), FBXL3-bound (cyan), and PER2-CBD-bound (gray) CRY.(A) Serine loop undergoes a large conformational change after PER2-CBD binding. (B and C) The interface loop and phosphate-binding loop are also sites of high structural plasticity. (D) Overall CRY-PHR showing the global structure adopts a common fold.DOI:http://dx.doi.org/10.7554/eLife.03674.013
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fig4s2: CRY-PHR superposition: including CRY1 apo (red), CRY2 apo (light blue), KL001-bound (green), FAD-bound (orange), FBXL3-bound (cyan), and PER2-CBD-bound (gray) CRY.(A) Serine loop undergoes a large conformational change after PER2-CBD binding. (B and C) The interface loop and phosphate-binding loop are also sites of high structural plasticity. (D) Overall CRY-PHR showing the global structure adopts a common fold.DOI:http://dx.doi.org/10.7554/eLife.03674.013

Mentions: In comparison to its FBXL3-, KL001-, and FAD-complexed forms, CRY2 adopts the same global fold when bound to PER2-CBD (Figure 4—figure supplement 2). The largest structural variations take place in two local regions, the interface loop next to the FAD-binding pocket and a serine-rich loop neighboring a secondary pocket (see below). The majority of PER2-contacting residues on CRY2 (85%) are strictly conserved between mammalian CRY1 and CRY2, suggesting that the two cryptochrome proteins share a common PER2 binding mode.


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)

CRY-PHR superposition: including CRY1 apo (red), CRY2 apo (light blue), KL001-bound (green), FAD-bound (orange), FBXL3-bound (cyan), and PER2-CBD-bound (gray) CRY.(A) Serine loop undergoes a large conformational change after PER2-CBD binding. (B and C) The interface loop and phosphate-binding loop are also sites of high structural plasticity. (D) Overall CRY-PHR showing the global structure adopts a common fold.DOI:http://dx.doi.org/10.7554/eLife.03674.013
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4157330&req=5

fig4s2: CRY-PHR superposition: including CRY1 apo (red), CRY2 apo (light blue), KL001-bound (green), FAD-bound (orange), FBXL3-bound (cyan), and PER2-CBD-bound (gray) CRY.(A) Serine loop undergoes a large conformational change after PER2-CBD binding. (B and C) The interface loop and phosphate-binding loop are also sites of high structural plasticity. (D) Overall CRY-PHR showing the global structure adopts a common fold.DOI:http://dx.doi.org/10.7554/eLife.03674.013
Mentions: In comparison to its FBXL3-, KL001-, and FAD-complexed forms, CRY2 adopts the same global fold when bound to PER2-CBD (Figure 4—figure supplement 2). The largest structural variations take place in two local regions, the interface loop next to the FAD-binding pocket and a serine-rich loop neighboring a secondary pocket (see below). The majority of PER2-contacting residues on CRY2 (85%) are strictly conserved between mammalian CRY1 and CRY2, suggesting that the two cryptochrome proteins share a common PER2 binding mode.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Washington, Seattle, United States.

Show MeSH
Related in: MedlinePlus