期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 17, 页码 6921-6926出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1014898107
关键词
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资金
- National Research Laboratory [NRL-2006-02287]
- Korea Research Foundation [KRF-2008-220-C00040]
- 21C Frontier Functional Proteomics Program [FPR08B2-270]
- Korea Healthcare Technology Research and Development Project [A092006]
- Ubiquitome Research Program [M105 33010001-05N3301-00100]
- Bio-MR research program
- Global Frontier Project [NRF-M1AXA002-2010-0029765]
- Grants-in-Aid for Scientific Research [22770106] Funding Source: KAKEN
- National Research Foundation of Korea [2008-220-C00040] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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 alpha and Z beta, and an adjacent putative B-DNA binding domain. The crystal structure of the Z beta domain of human DAI (hZ beta(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 beta(DAI), the solution structure of the free hZ beta(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 beta(DAI) has notable alterations in the alpha 3 recognition helix, the wing, and Y145, which are critical in Z-DNA recognition. Unlike some other Za domains, hZ beta(DAI) appears to have conformational flexibility, and structural adaptation is required for Z-DNA binding. Chemical-shift perturbation experiments revealed that hZ beta(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 beta(DAI) is likely to play an active role in binding to DNAs in both B and Z conformations in the recognition of foreign DNAs.
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