4ct0: Difference between revisions

Revision as of 07:31, 14 September 2022

Crystal Structure of Mouse Cryptochrome1 in Complex with Period2

Structural highlights

4ct0 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	CL, P6G, ZN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[CRY1_MOUSE] Blue light-dependent regulator of the circadian feedback loop. Inhibits CLOCK|NPAS2-ARNTL E box-mediated transcription. Acts, in conjunction with CRY2, in maintaining period length and circadian rhythmicity. Has no photolyase activity. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. May inhibit CLOCK|NPAS2-ARNTL transcriptional activity through stabilizing the unphosphorylated form of ARNTL.^[1] ^[2] ^[3]

Publication Abstract from PubMed

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.

Interaction of Circadian Clock Proteins CRY1 and PER2 Is Modulated by Zinc Binding and Disulfide Bond Formation.,Schmalen I, Reischl S, Wallach T, Klemz R, Grudziecki A, Prabu JR, Benda C, Kramer A, Wolf E Cell. 2014 May 22;157(5):1203-15. doi: 10.1016/j.cell.2014.03.057. PMID:24855952^[4]

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
↑ Kondratov RV, Kondratova AA, Lee C, Gorbacheva VY, Chernov MV, Antoch MP. Post-translational regulation of circadian transcriptional CLOCK(NPAS2)/BMAL1 complex by CRYPTOCHROMES. Cell Cycle. 2006 Apr;5(8):890-5. Epub 2006 Apr 17. PMID:16628007
↑ Chaves I, Yagita K, Barnhoorn S, Okamura H, van der Horst GT, Tamanini F. Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance. Mol Cell Biol. 2006 Mar;26(5):1743-53. PMID:16478995 doi:10.1128/MCB.26.5.1743-1753.2006
↑ Schmalen I, Reischl S, Wallach T, Klemz R, Grudziecki A, Prabu JR, Benda C, Kramer A, Wolf E. Interaction of Circadian Clock Proteins CRY1 and PER2 Is Modulated by Zinc Binding and Disulfide Bond Formation. Cell. 2014 May 22;157(5):1203-15. doi: 10.1016/j.cell.2014.03.057. PMID:24855952 doi:https://dx.doi.org/10.1016/j.cell.2014.03.057

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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

[2] Kondratov RV, Kondratova AA, Lee C, Gorbacheva VY, Chernov MV, Antoch MP. Post-translational regulation of circadian transcriptional CLOCK(NPAS2)/BMAL1 complex by CRYPTOCHROMES. Cell Cycle. 2006 Apr;5(8):890-5. Epub 2006 Apr 17. PMID:16628007

[3] Chaves I, Yagita K, Barnhoorn S, Okamura H, van der Horst GT, Tamanini F. Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance. Mol Cell Biol. 2006 Mar;26(5):1743-53. PMID:16478995 doi:10.1128/MCB.26.5.1743-1753.2006

[4] Schmalen I, Reischl S, Wallach T, Klemz R, Grudziecki A, Prabu JR, Benda C, Kramer A, Wolf E. Interaction of Circadian Clock Proteins CRY1 and PER2 Is Modulated by Zinc Binding and Disulfide Bond Formation. Cell. 2014 May 22;157(5):1203-15. doi: 10.1016/j.cell.2014.03.057. PMID:24855952 doi:https://dx.doi.org/10.1016/j.cell.2014.03.057

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[2]

[3]

[4]

@@ Line 3: / Line 3: @@
 <StructureSection load='4ct0' size='340' side='right'caption='[[4ct0]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ct0]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CT0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4CT0 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ct0]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4CT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4CT0 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4ct0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ct0 OCA], [http://pdbe.org/4ct0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ct0 RCSB], [http://www.ebi.ac.uk/pdbsum/4ct0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ct0 ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4ct0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ct0 OCA], [https://pdbe.org/4ct0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ct0 RCSB], [https://www.ebi.ac.uk/pdbsum/4ct0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ct0 ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/CRY1_MOUSE CRY1_MOUSE]] Blue light-dependent regulator of the circadian feedback loop. Inhibits CLOCK|NPAS2-ARNTL E box-mediated transcription. Acts, in conjunction with CRY2, in maintaining period length and circadian rhythmicity. Has no photolyase activity. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. May inhibit CLOCK|NPAS2-ARNTL transcriptional activity through stabilizing the unphosphorylated form of ARNTL.<ref>PMID:10428031</ref> <ref>PMID:16628007</ref> <ref>PMID:16478995</ref>  [[http://www.uniprot.org/uniprot/PER2_MOUSE 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.<ref>PMID:10428031</ref> <ref>PMID:17310242</ref>
+[[https://www.uniprot.org/uniprot/CRY1_MOUSE CRY1_MOUSE]] Blue light-dependent regulator of the circadian feedback loop. Inhibits CLOCK|NPAS2-ARNTL E box-mediated transcription. Acts, in conjunction with CRY2, in maintaining period length and circadian rhythmicity. Has no photolyase activity. Capable of translocating circadian clock core proteins such as PER proteins to the nucleus. May inhibit CLOCK|NPAS2-ARNTL transcriptional activity through stabilizing the unphosphorylated form of ARNTL.<ref>PMID:10428031</ref> <ref>PMID:16628007</ref> <ref>PMID:16478995</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 20: / Line 20: @@
 ==See Also==
-*[[Cryptochrome|Cryptochrome]]
+*[[Cryptochrome 3D structures|Cryptochrome 3D structures]]
 *[[Period circadian protein|Period circadian protein]]
 == References ==
@@ Line 27: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Benda, C]]
+[[Category: Benda C]]
-[[Category: Prabu, J Rajan]]
+[[Category: Rajan Prabu J]]
-[[Category: Schmalen, I]]
+[[Category: Schmalen I]]
-[[Category: Wolf, E]]
+[[Category: Wolf E]]
-[[Category: Circadian clock protein]]
-[[Category: Cryptochrome interaction]]
-[[Category: Cryptochrome-period complex]]
-[[Category: Disulfide bond]]
-[[Category: Redox regulation]]
-[[Category: Zinc interface]]

4ct0: Difference between revisions

Revision as of 07:31, 14 September 2022

Crystal Structure of Mouse Cryptochrome1 in Complex with Period2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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