2l4m
From Proteopedia
Solution structure of the Zbeta domain of human DAI and its binding modes to B- and Z-DNA
Structural highlights
FunctionZBP1_HUMAN Participates in the detection by the host's innate immune system of DNA from viral, bacterial or even host origin. Plays a role in host defense against tumors and pathogens. Acts as a cytoplasmic DNA sensor which, when activated, induces the recruitment of TBK1 and IRF3 to its C-terminal region and activates the downstream interferon regulatory factor (IRF) and NF-kappa B transcription factors, leading to type-I interferon production. ZBP1-induced NF-kappaB activation probably involves the recruitment of the RHIM containing kinases RIPK1 and RIPK3 (By similarity). Publication Abstract from PubMedThe 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), Zalpha and Zbeta, and an adjacent putative B-DNA binding domain. The crystal structure of the Zbeta domain of human DAI (hZbeta(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 hZbeta(DAI), the solution structure of the free hZbeta(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 hZbeta(DAI) has notable alterations in the alpha3 recognition helix, the "wing," and Y145, which are critical in Z-DNA recognition. Unlike some other Zalpha domains, hZbeta(DAI) appears to have conformational flexibility, and structural adaptation is required for Z-DNA binding. Chemical-shift perturbation experiments revealed that hZbeta(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, hZbeta(DAI) is likely to play an active role in binding to DNAs in both B and Z conformations in the recognition of foreign DNAs. Solution structure of the Zbeta domain of human DNA-dependent activator of IFN-regulatory factors and its binding modes to B- and Z-DNAs.,Kim K, Khayrutdinov BI, Lee CK, Cheong HK, Kang SW, Park H, Lee S, Kim YG, Jee J, Rich A, Kim KK, Jeon YH Proc Natl Acad Sci U S A. 2011 Apr 26;108(17):6921-6. Epub 2011 Apr 6. PMID:21471454[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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