TY - JOUR
T1 - Structure of the Vesicular Stomatitis Virus L Protein in Complex with Its Phosphoprotein Cofactor
AU - Jenni, Simon
AU - Bloyet, Louis Marie
AU - Diaz-Avalos, Ruben
AU - Liang, Bo
AU - Whelan, Sean P.J.
AU - Grigorieff, Nikolaus
AU - Harrison, Stephen C.
N1 - Funding Information:
We acknowledge support from NIH grant R37 AI059371 to S.P.J.W. N.G. and S.C.H. are investigators in the Howard Hughes Medical Institute.
Publisher Copyright:
© 2019 The Authors
PY - 2020/1/7
Y1 - 2020/1/7
N2 - The large (L) proteins of non-segmented, negative-strand RNA viruses are multifunctional enzymes that produce capped, methylated, and polyadenylated mRNA and replicate the viral genome. A phosphoprotein (P), required for efficient RNA-dependent RNA polymerization from the viral ribonucleoprotein (RNP) template, regulates the function and conformation of the L protein. We report the structure of vesicular stomatitis virus L in complex with its P cofactor determined by electron cryomicroscopy at 3.0 Å resolution, enabling us to visualize bound segments of P. The contacts of three P segments with multiple L domains show how P induces a closed, compact, initiation-competent conformation. Binding of P to L positions its N-terminal domain adjacent to a putative RNA exit channel for efficient encapsidation of newly synthesized genomes with the nucleoprotein and orients its C-terminal domain to interact with an RNP template. The model shows that a conserved tryptophan in the priming loop can support the initiating 5′ nucleotide. Jenni et al. describe a 3.0 Å resolution cryo-EM structure of vesicular stomatitis virus L protein, bound with its P-protein cofactor, suggesting molecular features of RNA-synthesis initiation, transcript capping, and replication-product encapsidation.
AB - The large (L) proteins of non-segmented, negative-strand RNA viruses are multifunctional enzymes that produce capped, methylated, and polyadenylated mRNA and replicate the viral genome. A phosphoprotein (P), required for efficient RNA-dependent RNA polymerization from the viral ribonucleoprotein (RNP) template, regulates the function and conformation of the L protein. We report the structure of vesicular stomatitis virus L in complex with its P cofactor determined by electron cryomicroscopy at 3.0 Å resolution, enabling us to visualize bound segments of P. The contacts of three P segments with multiple L domains show how P induces a closed, compact, initiation-competent conformation. Binding of P to L positions its N-terminal domain adjacent to a putative RNA exit channel for efficient encapsidation of newly synthesized genomes with the nucleoprotein and orients its C-terminal domain to interact with an RNP template. The model shows that a conserved tryptophan in the priming loop can support the initiating 5′ nucleotide. Jenni et al. describe a 3.0 Å resolution cryo-EM structure of vesicular stomatitis virus L protein, bound with its P-protein cofactor, suggesting molecular features of RNA-synthesis initiation, transcript capping, and replication-product encapsidation.
KW - antiviral
KW - ebola
KW - polymerase
KW - rabies
KW - respiratory syncytial virus
KW - rhabdoviruses
UR - http://www.scopus.com/inward/record.url?scp=85077457578&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2019.12.024
DO - 10.1016/j.celrep.2019.12.024
M3 - Article
C2 - 31914397
AN - SCOPUS:85077457578
SN - 2211-1247
VL - 30
SP - 53-60.e5
JO - Cell Reports
JF - Cell Reports
IS - 1
ER -