Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays
Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. Several viruses encode proteins containing bZIP domains, inclu...
| Main Authors: | , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Chemical Society
2011
|
| Online Access: | http://hdl.handle.net/1721.1/67686 https://orcid.org/0000-0003-4074-8980 |
| _version_ | 1811088262665601024 |
|---|---|
| author | Grigoryan, Gevorg Keating, Amy E. Reinke, Aaron W. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Grigoryan, Gevorg Keating, Amy E. Reinke, Aaron W. |
| author_sort | Grigoryan, Gevorg |
| collection | MIT |
| description | Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. Several viruses encode proteins containing bZIP domains, including four that encode bZIPs lacking significant homology to any human protein. We investigated the interaction specificity of these four viral bZIPs by using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs. The arrays recapitulated reported viral−human interactions and also uncovered new associations. MEQ and HBZ interacted with multiple human partners and had unique interaction profiles compared to any human bZIPs, whereas K-bZIP and BZLF1 displayed homospecificity. New interactions detected included HBZ with MAFB, MAFG, ATF2, CEBPG, and CREBZF and MEQ with NFIL3. These were confirmed in solution using circular dichroism. HBZ can heteroassociate with MAFB and MAFG in the presence of MARE-site DNA, and this interaction is dependent on the basic region of HBZ. NFIL3 and MEQ have different yet overlapping DNA-binding specificities and can form a heterocomplex with DNA. Computational design considering both affinity for MEQ and specificity with respect to other undesired bZIP-type interactions was used to generate a MEQ dimerization inhibitor. This peptide, anti-MEQ, bound MEQ both stably and specifically, as assayed using coiled-coil arrays and circular dichroism in solution. Anti-MEQ also inhibited MEQ binding to DNA. These studies can guide further investigation of the function of viral and human bZIP complexes. |
| first_indexed | 2024-09-23T13:59:22Z |
| format | Article |
| id | mit-1721.1/67686 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:59:22Z |
| publishDate | 2011 |
| publisher | American Chemical Society |
| record_format | dspace |
| spelling | mit-1721.1/676862022-09-28T17:32:28Z Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays Grigoryan, Gevorg Keating, Amy E. Reinke, Aaron W. Massachusetts Institute of Technology. Department of Biology Keating, Amy E. Keating, Amy E. Reinke, Aaron Wade Grigoryan, Gevorg Basic-region leucine-zipper transcription factors (bZIPs) contain a segment rich in basic amino acids that can bind DNA, followed by a leucine zipper that can interact with other leucine zippers to form coiled-coil homo- or heterodimers. Several viruses encode proteins containing bZIP domains, including four that encode bZIPs lacking significant homology to any human protein. We investigated the interaction specificity of these four viral bZIPs by using coiled-coil arrays to assess self-associations as well as heterointeractions with 33 representative human bZIPs. The arrays recapitulated reported viral−human interactions and also uncovered new associations. MEQ and HBZ interacted with multiple human partners and had unique interaction profiles compared to any human bZIPs, whereas K-bZIP and BZLF1 displayed homospecificity. New interactions detected included HBZ with MAFB, MAFG, ATF2, CEBPG, and CREBZF and MEQ with NFIL3. These were confirmed in solution using circular dichroism. HBZ can heteroassociate with MAFB and MAFG in the presence of MARE-site DNA, and this interaction is dependent on the basic region of HBZ. NFIL3 and MEQ have different yet overlapping DNA-binding specificities and can form a heterocomplex with DNA. Computational design considering both affinity for MEQ and specificity with respect to other undesired bZIP-type interactions was used to generate a MEQ dimerization inhibitor. This peptide, anti-MEQ, bound MEQ both stably and specifically, as assayed using coiled-coil arrays and circular dichroism in solution. Anti-MEQ also inhibited MEQ binding to DNA. These studies can guide further investigation of the function of viral and human bZIP complexes. National Institutes of Health (U.S.) (NIH Award GM067681) National Science Foundation (U.S.) (NSF Award 0216437) 2011-12-14T21:27:47Z 2011-12-14T21:27:47Z 2010-03 2010-01 Article http://purl.org/eprint/type/JournalArticle 0006-2960 1520-4995 http://hdl.handle.net/1721.1/67686 Reinke, Aaron W., Gevorg Grigoryan, and Amy E. Keating. “Identification of bZIP Interaction Partners of Viral Proteins HBZ, MEQ, BZLF1, and K-bZIP Using Coiled-Coil Arrays.” Biochemistry 49.9 (2010): 1985-1997. https://orcid.org/0000-0003-4074-8980 en_US http://dx.doi.org/10.1021/bi902065k Biochemistry Creative Commons Attribution-Noncommercial-Share Alike 3.0 http://creativecommons.org/licenses/by-nc-sa/3.0/ application/pdf American Chemical Society Prof. Amy Keating |
| spellingShingle | Grigoryan, Gevorg Keating, Amy E. Reinke, Aaron W. Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays |
| title | Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays |
| title_full | Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays |
| title_fullStr | Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays |
| title_full_unstemmed | Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays |
| title_short | Identification of bZIP interaction partners of viral proteins HBZ, MEQ, BZLF1, and K-bZIP using coiled-coil arrays |
| title_sort | identification of bzip interaction partners of viral proteins hbz meq bzlf1 and k bzip using coiled coil arrays |
| url | http://hdl.handle.net/1721.1/67686 https://orcid.org/0000-0003-4074-8980 |
| work_keys_str_mv | AT grigoryangevorg identificationofbzipinteractionpartnersofviralproteinshbzmeqbzlf1andkbzipusingcoiledcoilarrays AT keatingamye identificationofbzipinteractionpartnersofviralproteinshbzmeqbzlf1andkbzipusingcoiledcoilarrays AT reinkeaaronw identificationofbzipinteractionpartnersofviralproteinshbzmeqbzlf1andkbzipusingcoiledcoilarrays |