TY - JOUR
T1 - Visualizing molecular interactions that determine assembly of a bullet-shaped vesicular stomatitis virus particle
AU - Jenni, Simon
AU - Horwitz, Joshua A.
AU - Bloyet, Louis Marie
AU - Whelan, Sean P.J.
AU - Harrison, Stephen C.
N1 - Funding Information:
We thank Z. Li, S. Sterling, R. Walsh and S. Rawson for facilitating our use of the Harvard Medical School Cryo-EM Center for Structural Biology and the Harvard Medical School Molecular Electron Microscopy Suite; the Nancy Lurie Marks Family Foundation for support of the Cryo-EM Center; the SBGrid Advanced Research Computing group for IT support, and T. Kirchhausen for access to computational resources. Portions of this research were conducted on the O2 High Performance Compute Cluster, operated by the Research Computing Group at Harvard Medical School. We acknowledge support from NIH grants R37-AI1059371 (to S.P.J.W.) and R01-CA13202 (to S.C.H.). S.C.H. is an Investigator in the Howard Hughes Medical Institute.
Funding Information:
We thank Z. Li, S. Sterling, R. Walsh and S. Rawson for facilitating our use of the Harvard Medical School Cryo-EM Center for Structural Biology and the Harvard Medical School Molecular Electron Microscopy Suite; the Nancy Lurie Marks Family Foundation for support of the Cryo-EM Center; the SBGrid Advanced Research Computing group for IT support, and T. Kirchhausen for access to computational resources. Portions of this research were conducted on the O2 High Performance Compute Cluster, operated by the Research Computing Group at Harvard Medical School. We acknowledge support from NIH grants R37-AI1059371 (to S.P.J.W.) and R01-CA13202 (to S.C.H.). S.C.H. is an Investigator in the Howard Hughes Medical Institute.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with a non-segmented genome, closely related to rabies virus. Both have characteristic bullet-like shapes. We report the structure of intact, infectious VSV particles determined by cryogenic electron microscopy. By compensating for polymorphism among viral particles with computational classification, we obtained a reconstruction of the shaft (“trunk”) at 3.5 Å resolution, with lower resolution for the rounded tip. The ribonucleoprotein (RNP), genomic RNA complexed with nucleoprotein (N), curls into a dome-like structure with about eight gradually expanding turns before transitioning into the regular helical trunk. Two layers of matrix (M) protein link the RNP with the membrane. Radial inter-layer subunit contacts are fixed within single RNA-N-M1-M2 modules, but flexible lateral and axial interactions allow assembly of polymorphic virions. Together with published structures of recombinant N in various states, our results suggest a mechanism for membrane-coupled self-assembly of VSV and its relatives.
AB - Vesicular stomatitis virus (VSV) is a negative-strand RNA virus with a non-segmented genome, closely related to rabies virus. Both have characteristic bullet-like shapes. We report the structure of intact, infectious VSV particles determined by cryogenic electron microscopy. By compensating for polymorphism among viral particles with computational classification, we obtained a reconstruction of the shaft (“trunk”) at 3.5 Å resolution, with lower resolution for the rounded tip. The ribonucleoprotein (RNP), genomic RNA complexed with nucleoprotein (N), curls into a dome-like structure with about eight gradually expanding turns before transitioning into the regular helical trunk. Two layers of matrix (M) protein link the RNP with the membrane. Radial inter-layer subunit contacts are fixed within single RNA-N-M1-M2 modules, but flexible lateral and axial interactions allow assembly of polymorphic virions. Together with published structures of recombinant N in various states, our results suggest a mechanism for membrane-coupled self-assembly of VSV and its relatives.
UR - http://www.scopus.com/inward/record.url?scp=85135999561&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-32223-1
DO - 10.1038/s41467-022-32223-1
M3 - Article
C2 - 35970826
AN - SCOPUS:85135999561
SN - 2041-1723
VL - 13
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4802
ER -