| Functional motifs in the (6-4) photolyase crystal structure make a comparative framework for DNA repair photolyases and clock cryptochromes. | |
| | |
MedLine Citation:
|
PMID: 19359474 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Homologous flavoproteins from the photolyase (PHR)/cryptochrome (CRY) family use the FAD cofactor in PHRs to catalyze DNA repair and in CRYs to tune the circadian clock and control development. To help address how PHR/CRY members achieve these diverse functions, we determined the crystallographic structure of Arabidopsis thaliana (6-4) PHR (UVR3), which is strikingly (>65%) similar in sequence to human circadian clock CRYs. The structure reveals a substrate-binding cavity specific for the UV-induced DNA lesion, (6-4) photoproduct, and cofactor binding sites different from those of bacterial PHRs and consistent with distinct mechanisms for activities and regulation. Mutational analyses were combined with this prototypic structure for the (6-4) PHR/clock CRY cluster to identify structural and functional motifs: phosphate-binding and Pro-Lys-Leu protrusion motifs constricting access to the substrate-binding cavity above FAD, sulfur loop near the external end of the Trp electron-transfer pathway, and previously undefined C-terminal helix. Our results provide a detailed, unified framework for investigations of (6-4) PHRs and the mammalian CRYs. Conservation of key residues and motifs controlling FAD access and activities suggests that regulation of FAD redox properties and radical stability is essential not only for (6-4) photoproduct DNA repair, but also for circadian clock-regulating CRY functions. The structural and functional results reported here elucidate archetypal relationships within this flavoprotein family and suggest how PHRs and CRYs use local residue and cofactor tuning, rather than larger structural modifications, to achieve their diverse functions encompassing DNA repair, plant growth and development, and circadian clock regulation. |
| | |
Authors:
|
Kenichi Hitomi; Luciano DiTacchio; Andrew S Arvai; Junpei Yamamoto; Sang-Tae Kim; Takeshi Todo; John A Tainer; Shigenori Iwai; Satchidananda Panda; Elizabeth D Getzoff |
Related Documents
:
|
2325644 - A constitutive damage-specific dna-binding protein is synthesized at higher levels in u... 16176594 - Uv irradiation induces homologous recombination genes in the model archaeon, halobacter... 23345104 - Recognition of specific and nonspecific dna by human lactoferrin. 22976174 - Functions of single-strand dna-binding proteins in dna replication, recombination, and ... 10761004 - Direct radiation damage to crystalline dna: what is the source of unaltered base release? 2773514 - Anatomic viral detection is automated: the application of a robotic molecular pathology... |
Publication Detail:
|
Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-04-09 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 106 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2009 Apr |
Date Detail:
|
Created Date: 2009-05-06 Completed Date: 2009-06-05 Revised Date: 2010-12-06 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 6962-7 Citation Subset: IM |
Affiliation:
|
Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan. |
| Data Bank Information | |
Bank Name/Acc. No.:
|
PDB/3FY4 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Amino Acid Sequence Animals Arabidopsis / enzymology*, genetics Arabidopsis Proteins Binding Sites Circadian Rhythm* Conserved Sequence Cryptochromes Crystallography, X-Ray DNA Repair / genetics* DNA, Plant / genetics, metabolism* Deoxyribodipyrimidine Photo-Lyase / chemistry*, genetics, metabolism* Flavoproteins / genetics, metabolism* Hydrophobic and Hydrophilic Interactions Molecular Sequence Data Phosphates / chemistry, metabolism Phosphorylation Protein Structure, Tertiary Sequence Alignment |
| Grant Support | |
ID/Acronym/Agency:
|
1R32GM082083-01/GM/NIGMS NIH HHS; EY016807/EY/NEI NIH HHS; GM046312/GM/NIGMS NIH HHS; GM37684/GM/NIGMS NIH HHS; R01 GM037684-19/GM/NIGMS NIH HHS; R01 GM037684-20/GM/NIGMS NIH HHS; R01 GM037684-21/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Arabidopsis Proteins; 0/CRY1 protein, Arabidopsis; 0/Cryptochromes; 0/DNA, Plant; 0/Flavoproteins; 0/Phosphates; EC 4.1.99.-/pyrimidine(6-4)pyrimidone photolyase; EC 4.1.99.3/Deoxyribodipyrimidine Photo-Lyase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Inositol phosphatase SHIP1 is a primary target of miR-155.
Next Document: IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation.