Structure of full-length Drosophila cryptochrome

Brian D. Zoltowski, Anand T. Vaidya, Deniz Top, Joanne Widom, Michael W. Young, Brian R. Crane

Résultat de recherche: Articleexamen par les pairs

142 Citations (Scopus)

Résumé

The cryptochrome/photolyase (CRY/PL) family of photoreceptors mediates adaptive responses to ultraviolet and blue light exposure in all kingdoms of life. Whereas PLs function predominantly in DNA repair of cyclobutane pyrimidine dimers (CPDs) and 6-4 photolesions caused by ultraviolet radiation, CRYs transduce signals important for growth, development, magnetosensitivity and circadian clocks. Despite these diverse functions, PLs/CRYs preserve a common structural fold, a dependence on flavin adenine dinucleotide (FAD) and an internal photoactivation mechanism. However, members of the CRY/PL family differ in the substrates recognized (protein or DNA), photochemical reactions catalysed and involvement of an antenna cofactor. It is largely unknown how the animal CRYs that regulate circadian rhythms act on their substrates. CRYs contain a variable carboxy-terminal tail that appends the conserved PL homology domain (PHD) and is important for function. Here, we report a 2.3-Å resolution crystal structure of Drosophila CRY with an intact C terminus. The C-terminal helix docks in the analogous groove that binds DNA substrates in PLs. Conserved Trp 536 juts into the CRY catalytic centre to mimic PL recognition of DNA photolesions. The FAD anionic semiquinone found in the crystals assumes a conformation to facilitate restructuring of the tail helix. These results help reconcile the diverse functions of the CRY/PL family by demonstrating how conserved protein architecture and photochemistry can be elaborated into a range of light-driven functions.

Langue d'origineEnglish
Pages (de-à)396-399
Nombre de pages4
JournalNature
Volume480
Numéro de publication7377
DOI
Statut de publicationPublished - déc. 15 2011
Publié à l'externeOui

Note bibliographique

Funding Information:
Acknowledgements This study was supported by NIH Grant GM079679 to B.R.C. and GM054339 to M.W.Y. We thank the NE-CAT at the Advanced Photon Source of Argonne Laboratories for access to data collection facilities. We are indebted to C. Kemp for insect cell expression of dCRY and C. Manahan, X. Xu and W. Horne for their help with the ITC experiments.

ASJC Scopus Subject Areas

  • General

Empreinte numérique

Plonger dans les sujets de recherche 'Structure of full-length Drosophila cryptochrome'. Ensemble, ils forment une empreinte numérique unique.

Citer