PMID- 24855952
OWN - NLM
STAT- MEDLINE
DCOM- 20140723
LR  - 20140526
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Linking)
VI  - 157
IP  - 5
DP  - 2014 May 22
TI  - Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc 
      binding and disulfide bond formation.
PG  - 1203-15
LID - S0092-8674(14)00535-2 [pii]
LID - 10.1016/j.cell.2014.03.057 [doi]
AB  - 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.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Schmalen, Ira
AU  - Schmalen I
AD  - Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am 
      Klopferspitz 18, 82152 Martinsried/Munich, Germany.
FAU - Reischl, Silke
AU  - Reischl S
AD  - Laboratory of Chronobiology, Charite Universitatsmedizin Berlin, Hessische 
      Strasse 3-4, 10115 Berlin, Germany.
FAU - Wallach, Thomas
AU  - Wallach T
AD  - Laboratory of Chronobiology, Charite Universitatsmedizin Berlin, Hessische 
      Strasse 3-4, 10115 Berlin, Germany.
FAU - Klemz, Roman
AU  - Klemz R
AD  - Laboratory of Chronobiology, Charite Universitatsmedizin Berlin, Hessische 
      Strasse 3-4, 10115 Berlin, Germany.
FAU - Grudziecki, Astrid
AU  - Grudziecki A
AD  - Laboratory of Chronobiology, Charite Universitatsmedizin Berlin, Hessische 
      Strasse 3-4, 10115 Berlin, Germany.
FAU - Prabu, J Rajan
AU  - Prabu JR
AD  - Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am 
      Klopferspitz 18, 82152 Martinsried/Munich, Germany.
FAU - Benda, Christian
AU  - Benda C
AD  - Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am 
      Klopferspitz 18, 82152 Martinsried/Munich, Germany.
FAU - Kramer, Achim
AU  - Kramer A
AD  - Laboratory of Chronobiology, Charite Universitatsmedizin Berlin, Hessische 
      Strasse 3-4, 10115 Berlin, Germany. Electronic address: achim.kramer@charite.de.
FAU - Wolf, Eva
AU  - Wolf E
AD  - Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Am 
      Klopferspitz 18, 82152 Martinsried/Munich, Germany; Department of Physiological 
      Chemistry, Butenandt Institute, Ludwig Maximilians University of Munich, 
      Butenandtstrasse 5, 81377 Munich, Germany. Electronic address: 
      evawolf1@uni-mainz.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (Cry1 protein, mouse)
RN  - 0 (Cryptochromes)
RN  - 0 (F-Box Proteins)
RN  - 0 (Fbxl3 protein, mouse)
RN  - 0 (Per2 protein, mouse)
RN  - 0 (Period Circadian Proteins)
RN  - 0 (Recombinant Proteins)
RN  - J41CSQ7QDS (Zinc)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cryptochromes/*chemistry/*metabolism
MH  - *Crystallography, X-Ray
MH  - F-Box Proteins/chemistry/metabolism
MH  - Mice
MH  - Models, Molecular
MH  - Molecular Sequence Data
MH  - Period Circadian Proteins/*chemistry/*metabolism
MH  - Protein Interaction Domains and Motifs
MH  - Recombinant Proteins
MH  - Sequence Alignment
MH  - Zinc/metabolism
EDAT- 2014/05/27 06:00
MHDA- 2014/07/24 06:00
CRDT- 2014/05/27 06:00
PHST- 2013/09/04 00:00 [received]
PHST- 2014/02/06 00:00 [revised]
PHST- 2014/03/17 00:00 [accepted]
PHST- 2014/05/27 06:00 [entrez]
PHST- 2014/05/27 06:00 [pubmed]
PHST- 2014/07/24 06:00 [medline]
AID - S0092-8674(14)00535-2 [pii]
AID - 10.1016/j.cell.2014.03.057 [doi]
PST - ppublish
SO  - Cell. 2014 May 22;157(5):1203-15. doi: 10.1016/j.cell.2014.03.057.