Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation

Seung Won Yang, Yo Han Jang, Soon Bin Kwon, Yoon Jae Lee, Wonil Chae, Young Ho Byun, Paul Kim, Chan Park, Young Jae Lee, Choon Kang Kim, Young Seok Kim, Seong Il Choi, Baik Lin Seong

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

A novel protein-folding function of RNA has been recognized, which can outperform previously known molecular chaperone proteins.TheRNAas amolecular chaperone (chaperna) activity is intrinsic tosome ribozymesand is operational during viral infections.Our purposewasto testwhether influenzahemagglutinin (HA) canbe assembled in a soluble, trimeric, and immunologically activating conformation by means of an RNA molecular chaperone (chaperna) activity.AnRNA-interactingdomain (RID) fromthehostbeingimmunizedwas selected as adocking tag for RNAbinding,which served as a transducer for the chaperna function for de novo folding andtrimeric assembly ofRIDHA1. Mutations that affect tRNA binding greatly increased the soluble aggregation defective in trimer assembly, suggesting thatRNAinteraction critically controls thekinetic networkinthe folding/assemblypathway.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 relevantHA conformation. The results may be translated into a rapid response to anewinfluenzapandemic.Theharnessing of thenovel chaperna described herein with immunologically tailored antigen-folding functions should serve as a robust prophylactic and diagnostic tool for viral infections.

Original languageEnglish
Pages (from-to)2658-2675
Number of pages18
JournalFASEB Journal
Volume32
Issue number5
DOIs
Publication statusPublished - 2018 May

Fingerprint

Molecular Chaperones
Hemagglutinins
Virus Diseases
Human Influenza
Conformations
RNA
Nucleic Acid Conformation
Protein Folding
Hemagglutination
Transfer RNA
Neutralizing Antibodies
Transducers
Immunization
Protein folding
Antigens
Mutation
Agglomeration
Proteins
RID

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Yang, Seung Won ; Jang, Yo Han ; Kwon, Soon Bin ; Lee, Yoon Jae ; Chae, Wonil ; Byun, Young Ho ; Kim, Paul ; Park, Chan ; Lee, Young Jae ; Kang Kim, Choon ; 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. In: FASEB Journal. 2018 ; Vol. 32, No. 5. pp. 2658-2675.
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Yang, SW, Jang, YH, Kwon, SB, Lee, YJ, Chae, W, Byun, YH, Kim, P, Park, C, Lee, YJ, Kang Kim, C, Kim, YS, Choi, SI & Seong, BL 2018, 'Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation', FASEB Journal, vol. 32, no. 5, pp. 2658-2675. https://doi.org/10.1096/fj.201700747RR

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; Kang Kim, Choon; Kim, Young Seok; Choi, Seong Il; Seong, Baik Lin.

In: FASEB Journal, Vol. 32, No. 5, 05.2018, p. 2658-2675.

Research output: Contribution to journalArticle

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AU - Yang, Seung Won

AU - Jang, Yo Han

AU - Kwon, Soon Bin

AU - Lee, Yoon Jae

AU - Chae, Wonil

AU - Byun, Young Ho

AU - Kim, Paul

AU - Park, Chan

AU - Lee, Young Jae

AU - Kang Kim, Choon

AU - Kim, Young Seok

AU - Choi, Seong Il

AU - Seong, Baik Lin

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