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 journalArticlepeer-review

17 Citations (Scopus)


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
Issue number5
Publication statusPublished - 2018 May

Bibliographical note

Publisher Copyright:
© The Author(s) 2018.

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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