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10.1038/s41467-018-03503-6 http://scihub22266oqcxt.onion/10.1038/s41467-018-03503-6 C5859286!5859286 !29556064     free     free     free Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29556064 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Nat+Commun 2018 ; 9 (1 ): 1138 Nephropedia Template TP {{tp|p=29556064 |t=2018. An evolutionary hotspot defines functional differences between CRYPTOCHROMES |pdf=|usr=}}{{29556064 }} gab.com Text An evolutionary hotspot defines functional differences between CRYPTOCHROMES JO: Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=29556064 #FOAvip Mammalian circadian clocks are driven by a transcription/translation feedback loop composed of positive regulators (CLOCK/BMAL1) and repressors (CRYPTOCHROME 1/2 (CRY1/2) and PER1/2). To understand the structural principles of regulation, we used evolutionary sequence analysis to identify co-evolving residues within the CRY/PHL protein family. Here we report the identification of an ancestral secondary cofactor-binding pocket as an interface in repressive CRYs, mediating regulation through direct interaction with CLOCK and BMAL1. Mutations weakening binding between CLOCK/BMAL1 and CRY1 lead to acceleration of the clock, suggesting that subtle sequence divergences at this site can modulate clock function. Divergence between CRY1 and CRY2 at this site results in distinct periodic output. Weaker interactions between CRY2 and CLOCK/BMAL1 at this pocket are strengthened by co-expression of PER2, suggesting that PER expression limits the length of the repressive phase in CRY2-driven rhythms. Overall, this work provides a model for the mechanism and evolutionary variation of clock regulatory mechanisms. Twit Text FOAVip An evolutionary hotspot defines functional differences between CRYPTOCHROMES ????Nat Commun http://www.kidney.de/pget.php?&tw=1&pmid=29556064 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29556064 #FOAvip English Wikipedia <ref>{{Cite pmid|29556064 }}</ref> An evolutionary hotspot defines functional differences between CRYPTOCHROMES #MMPMID29556064 Rosensweig C ; Reynolds KA ; Gao P ; Laothamatas I ; Shan Y ; Ranganathan R ; Takahashi JS ; Green CB Nat Commun 2018[Mar]; 9 (1 ): 1138 PMID29556064 show ga Mammalian circadian clocks are driven by a transcription/translation feedback loop composed of positive regulators (CLOCK/BMAL1) and repressors (CRYPTOCHROME 1/2 (CRY1/2) and PER1/2). To understand the structural principles of regulation, we used evolutionary sequence analysis to identify co-evolving residues within the CRY/PHL protein family. Here we report the identification of an ancestral secondary cofactor-binding pocket as an interface in repressive CRYs, mediating regulation through direct interaction with CLOCK and BMAL1. Mutations weakening binding between CLOCK/BMAL1 and CRY1 lead to acceleration of the clock, suggesting that subtle sequence divergences at this site can modulate clock function. Divergence between CRY1 and CRY2 at this site results in distinct periodic output. Weaker interactions between CRY2 and CLOCK/BMAL1 at this pocket are strengthened by co-expression of PER2, suggesting that PER expression limits the length of the repressive phase in CRY2-driven rhythms. Overall, this work provides a model for the mechanism and evolutionary variation of clock regulatory mechanisms. |*Evolution, Molecular [MESH] |ARNTL Transcription Factors/chemistry/genetics/metabolism [MESH] |Allosteric Site/genetics [MESH] |Animals [MESH] |CLOCK Proteins/chemistry/genetics/metabolism [MESH] |Cell Line [MESH] |Circadian Clocks/genetics [MESH] |Cryptochromes/chemistry/*genetics/*metabolism [MESH] |HEK293 Cells [MESH] |Humans [MESH] |Insect Proteins/chemistry/genetics/metabolism [MESH] |Mice [MESH] |Mice, Knockout [MESH] |Models, Molecular [MESH] |Period Circadian Proteins/chemistry/genetics/metabolism [MESH] |Protein Interaction Domains and Motifs/genetics [MESH]An evolutionary hotspot defines functional differences between CRYPTOC(epmc).pdf DeepDyve Pubget Overpricing