Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype–anti-idiotype Fab complex
A detailed understanding of the fine specificity of serotype-specific human antibodies is vital for the development and evaluation of new vaccines for pathogenic flaviviruses such as dengue virus (DENV) and Zika virus. In this study, we thoroughly characterize the structural footprint of an anti-idi...
| Main Authors: | , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2018
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/88847 http://hdl.handle.net/10220/45924 |
| _version_ | 1824455501705904128 |
|---|---|
| author | Wong, Yee Hwa Goh, Boon Chong Lim, She Yah Teo, En Wei Lim, Angeline P. C. Dedon, Pete C. Hanson, Brendon J. MacAry, Paul A. Lescar, Julien |
| author2 | Jung, Jae U. |
| author_facet | Jung, Jae U. Wong, Yee Hwa Goh, Boon Chong Lim, She Yah Teo, En Wei Lim, Angeline P. C. Dedon, Pete C. Hanson, Brendon J. MacAry, Paul A. Lescar, Julien |
| author_sort | Wong, Yee Hwa |
| collection | NTU |
| description | A detailed understanding of the fine specificity of serotype-specific human antibodies is vital for the development and evaluation of new vaccines for pathogenic flaviviruses such as dengue virus (DENV) and Zika virus. In this study, we thoroughly characterize the structural footprint of an anti-idiotype antibody (E1) specific for a potent, fully human DENV serotype 1-specific antibody, termed HM14c10, derived from a recovered patient. The crystal structure at a resolution of 2.5 Å of a complex between the Fab fragments of E1 and HM14c10 provides the first detailed molecular comparison of an anti-idiotype paratope specific for a human antibody with its analogous epitope, a discontinuous quaternary structure located at the surface of the viral particle that spans adjacent envelope (E) proteins. This comparison reveals that the footprints left by E1 and E on HM14c10 largely overlap, explaining why the formation of binary complexes is mutually exclusive. Structural mimicry of the DENV E epitope by the E1 combining site is achieved via the formation of numerous interactions with heavy chain complementarity domain regions (CDRs) of HM14c10, while fewer interactions are observed with its light chain than for the E protein. We show that E1 can be utilized to detect HM14c10-like antibodies in sera from patients who recovered from DENV-1, infection suggesting that this is a public (common) idiotype. These data demonstrate the utility of employing an anti-idiotype antibody to monitor a patient's specific immune responses and suggest routes for the improvement of E “mimicry” by E1 by increasing its recognition of the Fab HM14c10 light chain CDRs. |
| first_indexed | 2025-02-19T03:39:13Z |
| format | Journal Article |
| id | ntu-10356/88847 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2025-02-19T03:39:13Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/888472023-02-28T16:58:04Z Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype–anti-idiotype Fab complex Wong, Yee Hwa Goh, Boon Chong Lim, She Yah Teo, En Wei Lim, Angeline P. C. Dedon, Pete C. Hanson, Brendon J. MacAry, Paul A. Lescar, Julien Jung, Jae U. School of Biological Sciences NTU Institute of Structural Biology DRNTU::Science::Biological sciences Dengue Virus Idiotypic Antibody A detailed understanding of the fine specificity of serotype-specific human antibodies is vital for the development and evaluation of new vaccines for pathogenic flaviviruses such as dengue virus (DENV) and Zika virus. In this study, we thoroughly characterize the structural footprint of an anti-idiotype antibody (E1) specific for a potent, fully human DENV serotype 1-specific antibody, termed HM14c10, derived from a recovered patient. The crystal structure at a resolution of 2.5 Å of a complex between the Fab fragments of E1 and HM14c10 provides the first detailed molecular comparison of an anti-idiotype paratope specific for a human antibody with its analogous epitope, a discontinuous quaternary structure located at the surface of the viral particle that spans adjacent envelope (E) proteins. This comparison reveals that the footprints left by E1 and E on HM14c10 largely overlap, explaining why the formation of binary complexes is mutually exclusive. Structural mimicry of the DENV E epitope by the E1 combining site is achieved via the formation of numerous interactions with heavy chain complementarity domain regions (CDRs) of HM14c10, while fewer interactions are observed with its light chain than for the E protein. We show that E1 can be utilized to detect HM14c10-like antibodies in sera from patients who recovered from DENV-1, infection suggesting that this is a public (common) idiotype. These data demonstrate the utility of employing an anti-idiotype antibody to monitor a patient's specific immune responses and suggest routes for the improvement of E “mimicry” by E1 by increasing its recognition of the Fab HM14c10 light chain CDRs. NRF (Natl Research Foundation, S’pore) MOE (Min. of Education, S’pore) NMRC (Natl Medical Research Council, S’pore) Published version 2018-09-11T02:31:12Z 2019-12-06T17:12:11Z 2018-09-11T02:31:12Z 2019-12-06T17:12:11Z 2017 Journal Article Wong, Y. H., Goh, B. C., Lim, S. Y., Teo, E. W., Lim, A. P. C., Dedon, P. C., . . . Lescar, J. (2017). Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype–anti-idiotype Fab complex. Journal of Virology, 91(17), e00406-17-. doi:10.1128/JVI.00406-17- 0022-538X https://hdl.handle.net/10356/88847 http://hdl.handle.net/10220/45924 10.1128/JVI.00406-17 en Journal of Virology © 2017 American Society for Microbiology. This paper was published in Journal of Virology and is made available as an electronic reprint (preprint) with permission of American Society for Microbiology. The published version is available at: [http://dx.doi.org/10.1128/JVI.00406-17]. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper is prohibited and is subject to penalties under law. 12 p. application/pdf |
| spellingShingle | DRNTU::Science::Biological sciences Dengue Virus Idiotypic Antibody Wong, Yee Hwa Goh, Boon Chong Lim, She Yah Teo, En Wei Lim, Angeline P. C. Dedon, Pete C. Hanson, Brendon J. MacAry, Paul A. Lescar, Julien Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype–anti-idiotype Fab complex |
| title | Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype–anti-idiotype Fab complex |
| title_full | Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype–anti-idiotype Fab complex |
| title_fullStr | Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype–anti-idiotype Fab complex |
| title_full_unstemmed | Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype–anti-idiotype Fab complex |
| title_short | Structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype–anti-idiotype Fab complex |
| title_sort | structural mimicry of the dengue virus envelope glycoprotein revealed by the crystallographic study of an idiotype anti idiotype fab complex |
| topic | DRNTU::Science::Biological sciences Dengue Virus Idiotypic Antibody |
| url | https://hdl.handle.net/10356/88847 http://hdl.handle.net/10220/45924 |
| work_keys_str_mv | AT wongyeehwa structuralmimicryofthedenguevirusenvelopeglycoproteinrevealedbythecrystallographicstudyofanidiotypeantiidiotypefabcomplex AT gohboonchong structuralmimicryofthedenguevirusenvelopeglycoproteinrevealedbythecrystallographicstudyofanidiotypeantiidiotypefabcomplex AT limsheyah structuralmimicryofthedenguevirusenvelopeglycoproteinrevealedbythecrystallographicstudyofanidiotypeantiidiotypefabcomplex AT teoenwei structuralmimicryofthedenguevirusenvelopeglycoproteinrevealedbythecrystallographicstudyofanidiotypeantiidiotypefabcomplex AT limangelinepc structuralmimicryofthedenguevirusenvelopeglycoproteinrevealedbythecrystallographicstudyofanidiotypeantiidiotypefabcomplex AT dedonpetec structuralmimicryofthedenguevirusenvelopeglycoproteinrevealedbythecrystallographicstudyofanidiotypeantiidiotypefabcomplex AT hansonbrendonj structuralmimicryofthedenguevirusenvelopeglycoproteinrevealedbythecrystallographicstudyofanidiotypeantiidiotypefabcomplex AT macarypaula structuralmimicryofthedenguevirusenvelopeglycoproteinrevealedbythecrystallographicstudyofanidiotypeantiidiotypefabcomplex AT lescarjulien structuralmimicryofthedenguevirusenvelopeglycoproteinrevealedbythecrystallographicstudyofanidiotypeantiidiotypefabcomplex |