Solution structure of the Z beta domain of human DNA-dependent activator of IFN-regulatory factors and its binding modes to B- and Z-DNAs
- Authors
- Kim, Kyungmin; Khayrutdinov, Bulat I.; Lee, Chung-Kyung; Cheong, Hae-Kap; Kang, Sung Wook; Park, Hyejin; Lee, Sangho; Kim, Yang-Gyun; Jee, JunGoo; Rich, Alexander; Kim, Kyeong Kyu; Jeon, Young Ho
- Issue Date
- 26-4월-2011
- Publisher
- NATL ACAD SCIENCES
- Citation
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.108, no.17, pp.6921 - 6926
- Indexed
- SCIE
SCOPUS
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 108
- Number
- 17
- Start Page
- 6921
- End Page
- 6926
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/112632
- DOI
- 10.1073/pnas.1014898107
- ISSN
- 0027-8424
- Abstract
- 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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Collections - College of Pharmacy > Department of Pharmaceutical Science > 1. Journal Articles
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