Assembly and cryo-EM structures of RNA-specific measles virus nucleocapsids provide mechanistic insight into paramyxoviral replication

Proceedings of the National Academy of Sciences of the United States of America
Ambroise DesfossesMartin Blackledge

Abstract

Assembly of paramyxoviral nucleocapsids on the RNA genome is an essential step in the viral cycle. The structural basis of this process has remained obscure due to the inability to control encapsidation. We used a recently developed approach to assemble measles virus nucleocapsid-like particles on specific sequences of RNA hexamers (poly-Adenine and viral genomic 5') in vitro, and determined their cryoelectron microscopy maps to 3.3-Å resolution. The structures unambiguously determine 5' and 3' binding sites and thereby the binding-register of viral genomic RNA within nucleocapsids. This observation reveals that the 3' end of the genome is largely exposed in fully assembled measles nucleocapsids. In particular, the final three nucleotides of the genome are rendered accessible to the RNA-dependent RNA polymerase complex, possibly enabling efficient RNA processing. The structures also reveal local and global conformational changes in the nucleoprotein upon assembly, in particular involving helix α6 and helix α13 that form edges of the RNA binding groove. Disorder is observed in the bound RNA, localized at one of the two backbone conformational switch sites. The high-resolution structure allowed us to identify putative nucleobase ...Continue Reading

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Citations

Dec 12, 2019·The Journal of Biological Chemistry·Yunrong GaoBo Liang
Jan 18, 2020·The Journal of Biological Chemistry·Chanakha K NavaratnarajahRoberto Cattaneo
Sep 10, 2019·Frontiers in Microbiology·Serafima GusevaRob W H Ruigrok
Apr 8, 2020·The Journal of Biological Chemistry·Angelo TotoStefano Gianni
Nov 6, 2020·PLoS Pathogens·Irina GutscheDaniel Kolakofsky
Jul 22, 2019·Archives of Biochemistry and Biophysics·Angelo TotoStefano Gianni
Apr 24, 2021·Communications Biology·Na ZhangQing-Tao Shen
Jun 6, 2021·Journal of Structural Biology·Luca ZinzulaWolfgang Baumeister
Jul 17, 2021·PLoS Pathogens·De-Sheng KerAlfred A Antson
Jul 4, 2021·Communications Biology·Hong ShanQing-Tao Shen

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