Solution Structure of the Zbeta Domain of Human DAI and Its Binding Modes to B- and Z-DNAs
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)...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
| Published: |
National Academy of Sciences (U.S.)
2011
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| Online Access: | http://hdl.handle.net/1721.1/66977 |
| _version_ | 1826216253473161216 |
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| author | 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 |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology 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 |
| author_sort | Kim, Kyungmin |
| collection | MIT |
| description | 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), Zα and Zβ, and an adjacent putative B-DNA binding domain. The crystal structure of the Zβ domain of human DAI (hZβDAI) 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 hZβDAI, the solution structure of the free hZβDAI 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 hZβDAI has notable alterations in the α3 recognition helix, the “wing,” and Y145, which are critical in Z-DNA recognition. Unlike some other Zα domains, hZβDAI appears to have conformational flexibility, and structural adaptation is required for Z-DNA binding. Chemical-shift perturbation experiments revealed that hZβDAI 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, hZβDAI is likely to play an active role in binding to DNAs in both B and Z conformations in the recognition of foreign DNAs. |
| first_indexed | 2024-09-23T16:44:46Z |
| format | Article |
| id | mit-1721.1/66977 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T16:44:46Z |
| publishDate | 2011 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/669772022-09-29T21:11:48Z Solution Structure of the Zbeta Domain of Human DAI and Its Binding Modes to B- and Z-DNAs Solution Structure of the Zβ Domain of Human DAI and Its Binding Modes to B- and Z-DNAs 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 Massachusetts Institute of Technology. Department of Biology Rich, Alexander Rich, Alexander 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), Zα and Zβ, and an adjacent putative B-DNA binding domain. The crystal structure of the Zβ domain of human DAI (hZβDAI) 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 hZβDAI, the solution structure of the free hZβDAI 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 hZβDAI has notable alterations in the α3 recognition helix, the “wing,” and Y145, which are critical in Z-DNA recognition. Unlike some other Zα domains, hZβDAI appears to have conformational flexibility, and structural adaptation is required for Z-DNA binding. Chemical-shift perturbation experiments revealed that hZβDAI 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, hZβDAI is likely to play an active role in binding to DNAs in both B and Z conformations in the recognition of foreign DNAs. Korea (South). Ministry of Science and Technology (National Research Laboratory Program (NRL-2006-02287)) Korea Research Foundation (grant KRF-2008-220-C00040) Korea (South). Ministry of Science and Technology (21C Frontier Functional Proteomics Program (FPR08B2-270)) Korea Research Foundation (Korea Healthcare Technology Research and Development Project (A092006)) Korea Research Foundation (Ubiquitome Research Program (M105 33010001- 05N3301-00100)) Global Frontier Project (Grant NRF-M1AXA002-2010-0029765) Bio-MR Research Program 2011-11-09T19:02:36Z 2011-11-09T19:02:36Z 2011-04 2010-10 Article http://purl.org/eprint/type/JournalArticle 1091-6490 http://hdl.handle.net/1721.1/66977 Kim, K. et al. “Solution structure of the Z domain of human DNA-dependent activator of IFN-regulatory factors and its binding modes to B- and Z-DNAs.” Proceedings of the National Academy of Sciences 108 (2011): 6921-6926. ©2011 by the National Academy of Sciences. en_US http://dx.doi.org/10.1073/pnas.1014898107 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | 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 Solution Structure of the Zbeta Domain of Human DAI and Its Binding Modes to B- and Z-DNAs |
| title | Solution Structure of the Zbeta Domain of Human DAI and Its Binding Modes to B- and Z-DNAs |
| title_full | Solution Structure of the Zbeta Domain of Human DAI and Its Binding Modes to B- and Z-DNAs |
| title_fullStr | Solution Structure of the Zbeta Domain of Human DAI and Its Binding Modes to B- and Z-DNAs |
| title_full_unstemmed | Solution Structure of the Zbeta Domain of Human DAI and Its Binding Modes to B- and Z-DNAs |
| title_short | Solution Structure of the Zbeta Domain of Human DAI and Its Binding Modes to B- and Z-DNAs |
| title_sort | solution structure of the zbeta domain of human dai and its binding modes to b and z dnas |
| url | http://hdl.handle.net/1721.1/66977 |
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