tetano
Editor, Senior Moderator
FASEB J. 2018 Jan 2. pii: fj.201700747RR. doi: 10.1096/fj.201700747RR. [Epub ahead of print]
[h=1]Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation.[/h] Yang SW[SUP]1[/SUP], Jang YH[SUP]1[/SUP], Kwon SB[SUP]1[/SUP], Lee YJ[SUP]1[/SUP], Chae W[SUP]1[/SUP], Byun YH[SUP]1[/SUP], Kim P[SUP]1[/SUP], Park C[SUP]1[/SUP], Lee YJ[SUP]1[/SUP], Kim CK[SUP]1[/SUP], Kim YS[SUP]1[/SUP], Choi SI[SUP]2[/SUP], Seong BL[SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] chaperna; neutralizing antibody; protein folding; viral infection
PMID: 29295864 DOI: 10.1096/fj.201700747RR
[h=1]Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation.[/h] Yang SW[SUP]1[/SUP], Jang YH[SUP]1[/SUP], Kwon SB[SUP]1[/SUP], Lee YJ[SUP]1[/SUP], Chae W[SUP]1[/SUP], Byun YH[SUP]1[/SUP], Kim P[SUP]1[/SUP], Park C[SUP]1[/SUP], Lee YJ[SUP]1[/SUP], Kim CK[SUP]1[/SUP], Kim YS[SUP]1[/SUP], Choi SI[SUP]2[/SUP], Seong BL[SUP]3,[/SUP][SUP]4[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
[h=4]KEYWORDS:[/h] chaperna; neutralizing antibody; protein folding; viral infection
PMID: 29295864 DOI: 10.1096/fj.201700747RR