Cargando…
Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation
A novel protein-folding function of RNA has been recognized, which can outperform previously known molecular chaperone proteins. The RNA as a molecular chaperone (chaperna) activity is intrinsic to some ribozymes and is operational during viral infections. Our purpose was to test whether influenza h...
Autores principales: | , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Federation of American Societies for Experimental Biology
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901386/ https://www.ncbi.nlm.nih.gov/pubmed/29295864 http://dx.doi.org/10.1096/fj.201700747RR |
_version_ | 1783314606345682944 |
---|---|
author | Yang, Seung Won Jang, Yo Han Kwon, Soon Bin Lee, Yoon Jae Chae, Wonil Byun, Young Ho Kim, Paul Park, Chan Lee, Young Jae Kim, Choon Kang Kim, Young Seok Choi, Seong Il Seong, Baik Lin |
author_facet | Yang, Seung Won Jang, Yo Han Kwon, Soon Bin Lee, Yoon Jae Chae, Wonil Byun, Young Ho Kim, Paul Park, Chan Lee, Young Jae Kim, Choon Kang Kim, Young Seok Choi, Seong Il Seong, Baik Lin |
author_sort | Yang, Seung Won |
collection | PubMed |
description | A novel protein-folding function of RNA has been recognized, which can outperform previously known molecular chaperone proteins. The RNA as a molecular chaperone (chaperna) activity is intrinsic to some ribozymes and is operational during viral infections. Our purpose was to test whether influenza hemagglutinin (HA) can be assembled in a soluble, trimeric, and immunologically activating conformation by means of an RNA molecular chaperone (chaperna) activity. An RNA-interacting domain (RID) from the host being immunized was selected as a docking tag for RNA binding, which served as a transducer for the chaperna function for de novo folding and trimeric assembly of RID-HA1. Mutations that affect tRNA binding greatly increased the soluble aggregation defective in trimer assembly, suggesting that RNA interaction critically controls the kinetic network in the folding/assembly pathway. Immunization of mice resulted in strong hemagglutination inhibition and high titers of a neutralizing antibody, providing sterile protection against a lethal challenge and confirming the immunologically relevant HA conformation. The results may be translated into a rapid response to a new influenza pandemic. The harnessing of the novel chaperna described herein with immunologically tailored antigen-folding functions should serve as a robust prophylactic and diagnostic tool for viral infections.—Yang, S. W., Jang, Y. H., Kwon, S. B., Lee, Y. J., Chae, W., Byun, Y. H., Kim, P., Park, C., Lee, Y. J., Kim, C. K., Kim, Y. S., Choi, S. I., Seong, B. L. Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation. |
format | Online Article Text |
id | pubmed-5901386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Federation of American Societies for Experimental Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-59013862018-04-19 Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation Yang, Seung Won Jang, Yo Han Kwon, Soon Bin Lee, Yoon Jae Chae, Wonil Byun, Young Ho Kim, Paul Park, Chan Lee, Young Jae Kim, Choon Kang Kim, Young Seok Choi, Seong Il Seong, Baik Lin FASEB J Research A novel protein-folding function of RNA has been recognized, which can outperform previously known molecular chaperone proteins. The RNA as a molecular chaperone (chaperna) activity is intrinsic to some ribozymes and is operational during viral infections. Our purpose was to test whether influenza hemagglutinin (HA) can be assembled in a soluble, trimeric, and immunologically activating conformation by means of an RNA molecular chaperone (chaperna) activity. An RNA-interacting domain (RID) from the host being immunized was selected as a docking tag for RNA binding, which served as a transducer for the chaperna function for de novo folding and trimeric assembly of RID-HA1. Mutations that affect tRNA binding greatly increased the soluble aggregation defective in trimer assembly, suggesting that RNA interaction critically controls the kinetic network in the folding/assembly pathway. Immunization of mice resulted in strong hemagglutination inhibition and high titers of a neutralizing antibody, providing sterile protection against a lethal challenge and confirming the immunologically relevant HA conformation. The results may be translated into a rapid response to a new influenza pandemic. The harnessing of the novel chaperna described herein with immunologically tailored antigen-folding functions should serve as a robust prophylactic and diagnostic tool for viral infections.—Yang, S. W., Jang, Y. H., Kwon, S. B., Lee, Y. J., Chae, W., Byun, Y. H., Kim, P., Park, C., Lee, Y. J., Kim, C. K., Kim, Y. S., Choi, S. I., Seong, B. L. Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation. Federation of American Societies for Experimental Biology 2018-05 2018-01-08 /pmc/articles/PMC5901386/ /pubmed/29295864 http://dx.doi.org/10.1096/fj.201700747RR Text en © The Author(s) http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) (http://creativecommons.org/licenses/by-nc/4.0/) which permits noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Yang, Seung Won Jang, Yo Han Kwon, Soon Bin Lee, Yoon Jae Chae, Wonil Byun, Young Ho Kim, Paul Park, Chan Lee, Young Jae Kim, Choon Kang Kim, Young Seok Choi, Seong Il Seong, Baik Lin Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation |
title | Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation |
title_full | Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation |
title_fullStr | Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation |
title_full_unstemmed | Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation |
title_short | Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation |
title_sort | harnessing an rna-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5901386/ https://www.ncbi.nlm.nih.gov/pubmed/29295864 http://dx.doi.org/10.1096/fj.201700747RR |
work_keys_str_mv | AT yangseungwon harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT jangyohan harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT kwonsoonbin harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT leeyoonjae harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT chaewonil harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT byunyoungho harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT kimpaul harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT parkchan harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT leeyoungjae harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT kimchoonkang harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT kimyoungseok harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT choiseongil harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation AT seongbaiklin harnessinganrnamediatedchaperonefortheassemblyofinfluenzahemagglutinininanimmunologicallyrelevantconformation |