4CT0

Crystal Structure of Mouse Cryptochrome1 in Complex with Period2

Summary for 4CT0

• Entry DOI: 10.2210/pdb4ct0/pdb
• Descriptor: CRYPTOCHROME-1, PERIOD CIRCADIAN PROTEIN HOMOLOG 2, ZINC ION, ... (6 entities in total)
• Functional Keywords: circadian clock protein, cryptochrome-period complex, cryptochrome interactions, zinc interface, disulfide bond, redox regulation
• Biological source: MUS MUSCULUS (HOUSE MOUSE); More
• Cellular location: Cytoplasm: P97784; Nucleus: O54943
• Total number of polymer chains: 2
• Total formula weight: 75197.45

Authors

Schmalen, I.,Rajan Prabu, J.,Benda, C.,Wolf, E. (deposition date: 2014-03-11, release date: 2014-06-04, Last modification date: 2023-12-20)

Primary citation

Schmalen, I.,Reischl, S.,Wallach, T.,Klemz, R.,Grudziecki, A.,Prabu, J.R.,Benda, C.,Kramer, A.,Wolf, E.
Interaction of Circadian Clock Proteins Cry1 and Per2 is Modulated by Zinc Binding and Disulfide Bond Formation.
Cell(Cambridge,Mass.), 157:1203-, 2014

PubMed 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.

PubMed: 24855952
DOI: 10.1016/J.CELL.2014.03.057

Experimental method

X-RAY DIFFRACTION (2.45 Å)