English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Interaction of Circadian Clock Proteins CRY1 and PER2 Is Modulated by Zinc Binding and Disulfide Bond Formation

MPS-Authors
/persons/resource/persons78641

Schmalen,  Ira
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons131140

Prabu,  J. Rajan
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons77736

Benda,  Christian
Conti, Elena / Structural Cell Biology, Max Planck Institute of Biochemistry, Max Planck Society;

/persons/resource/persons78899

Wolf,  Eva
Former Research Groups, Max Planck Institute of Biochemistry, Max Planck Society;

External Ressource
No external resources are shared
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Schmalen, I., Reischl, S., Wallach, T., Klemz, R., Grudziecki, A., Prabu, J. R., et al. (2014). Interaction of Circadian Clock Proteins CRY1 and PER2 Is Modulated by Zinc Binding and Disulfide Bond Formation. CELL, 157(5), 1203-1215. doi:10.1016/j.cell.2014.03.057.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0019-CF0E-E
Abstract
Period (PER) proteins are essential components of the mammalian circadian clock. They form complexes with cryptochromes (CRY), which negatively regulate CLOCK/BMAL1-dependent transactivation of clock and clock-controlled genes. To define the roles of mammalian CRY/PER complexes in the circadian clock, we have determined the crystal structure of a complex comprising the photolyase homology region of mouse CRY1 (mCRY1) and a C-terminal mouse PER2 (mPER2) fragment. mPER2 winds around the helical mCRY1 domain covering the binding sites of FBXL3 and CLOCK/BMAL1, but not the FAD binding pocket. Our structure revealed an unexpected zinc ion in one interface, which stabilizes mCRY1-mPER2 interactions in vivo. We provide evidence that mCRY1/mPER2 complex formation is modulated by an interplay of zinc binding and mCRY1 disulfide bond formation, which may be influenced by the redox state of the cell. Our studies may allow for the development of circadian and metabolic modulators.