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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2011-4-27
pubmed:databankReference
pubmed:abstractText
The DNA-dependent activator of IFN-regulatory factors (DAI), also known as DLM-1/ZBP1, initiates an innate immune response by binding to foreign DNAs in the cytosol. For full activation of the immune response, three DNA binding domains at the N terminus are required: two Z-DNA binding domains (ZBDs), Z? and Z?, and an adjacent putative B-DNA binding domain. The crystal structure of the Z? domain of human DAI (hZ?(DAI)) in complex with Z-DNA revealed structural features distinct from other known Z-DNA binding proteins, and it was classified as a group II ZBD. To gain structural insights into the DNA binding mechanism of hZ?(DAI), the solution structure of the free hZ?(DAI) was solved, and its bindings to B- and Z-DNAs were analyzed by NMR spectroscopy. Compared to the Z-DNA-bound structure, the conformation of free hZ?(DAI) has notable alterations in the ?3 recognition helix, the "wing," and Y145, which are critical in Z-DNA recognition. Unlike some other Z? domains, hZ?(DAI) appears to have conformational flexibility, and structural adaptation is required for Z-DNA binding. Chemical-shift perturbation experiments revealed that hZ?(DAI) also binds weakly to B-DNA via a different binding mode. The C-terminal domain of DAI is reported to undergo a conformational change on B-DNA binding; thus, it is possible that these changes are correlated. During the innate immune response, hZ?(DAI) is likely to play an active role in binding to DNAs in both B and Z conformations in the recognition of foreign DNAs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1091-6490
pubmed:author
pubmed:issnType
Electronic
pubmed:day
26
pubmed:volume
108
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6921-6
pubmed:dateRevised
2011-10-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Solution structure of the Zbeta domain of human DNA-dependent activator of IFN-regulatory factors and its binding modes to B- and Z-DNAs.
pubmed:affiliation
Department of Molecular Cell Biology, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea. kkim@med.skku.ac.kr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't