Document Detail


Flavin reduction activates Drosophila cryptochrome.
MedLine Citation:
PMID:  24297896     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Entrainment of circadian rhythms in higher organisms relies on light-sensing proteins that communicate to cellular oscillators composed of delayed transcriptional feedback loops. The principal photoreceptor of the fly circadian clock, Drosophila cryptochrome (dCRY), contains a C-terminal tail (CTT) helix that binds beside a FAD cofactor and is essential for light signaling. Light reduces the dCRY FAD to an anionic semiquinone (ASQ) radical and increases CTT proteolytic susceptibility but does not lead to CTT chemical modification. Additional changes in proteolytic sensitivity and small-angle X-ray scattering define a conformational response of the protein to light that centers at the CTT but also involves regions remote from the flavin center. Reduction of the flavin is kinetically coupled to CTT rearrangement. Chemical reduction to either the ASQ or the fully reduced hydroquinone state produces the same conformational response as does light. The oscillator protein Timeless (TIM) contains a sequence similar to the CTT; the corresponding peptide binds dCRY in light and protects the flavin from oxidation. However, TIM mutants therein still undergo dCRY-mediated degradation. Thus, photoreduction to the ASQ releases the dCRY CTT and promotes binding to at least one region of TIM. Flavin reduction by either light or cellular reductants may be a general mechanism of CRY activation.
Authors:
Anand T Vaidya; Deniz Top; Craig C Manahan; Joshua M Tokuda; Sheng Zhang; Lois Pollack; Michael W Young; Brian R Crane
Related Documents :
16611836 - Twitch and tetanic properties of human thenar motor units paralyzed by chronic spinal c...
24554316 - Senior living environments: evidence-based lighting design strategies.
18984046 - The effect of difference frequency on electrocommunication: chirp production and encodi...
22056856 - Dosimetric evaluation of breast radiotherapy in a dynamic phantom.
7900296 - Restricted ability to recover three-dimensional global motion from one-dimensional loca...
21974196 - Monotic versus diotic thresholds in an amplitude modulation and quasi-frequency modulat...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-12-02
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  110     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2013 Dec 
Date Detail:
Created Date:  2013-12-18     Completed Date:  2014-02-24     Revised Date:  2014-11-06    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  20455-60     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Circadian Clocks / physiology,  radiation effects
Cryptochromes / chemistry,  genetics,  metabolism*
Drosophila Proteins / chemistry,  genetics,  metabolism*
Drosophila melanogaster
Eye Proteins / chemistry,  genetics,  metabolism*
Flavin-Adenine Dinucleotide / chemistry,  genetics,  metabolism*
Light
Oxidation-Reduction / radiation effects
Protein Binding / physiology,  radiation effects
Signal Transduction / physiology*,  radiation effects
Grant Support
ID/Acronym/Agency:
GM054339/GM/NIGMS NIH HHS; GM079679/GM/NIGMS NIH HHS; P41 GM103485/GM/NIGMS NIH HHS; R01 GM079679/GM/NIGMS NIH HHS; R37 GM054339/GM/NIGMS NIH HHS; T32 GM008500/GM/NIGMS NIH HHS; TMGM008267//PHS HHS
Chemical
Reg. No./Substance:
0/Cryptochromes; 0/Drosophila Proteins; 0/Eye Proteins; 0/cryptochrome protein, Drosophila; 0/timeless protein, Drosophila; 146-14-5/Flavin-Adenine Dinucleotide
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  A maximum entropy framework for nonexponential distributions.
Next Document:  Dexras1 mediates glucocorticoid-associated adipogenesis and diet-induced obesity.