title: Structure of the L Protein of Vesicular Stomatitis Virus from Electron Cryomicroscopy.
abstract: The large (L) proteins of non-segmented, negative-strand RNA viruses, a group that includes Ebola and rabies viruses, catalyze RNA-dependent RNA polymerization with viral ribonucleoprotein as template, a non-canonical sequence of capping and methylation reactions, and polyadenylation of viral messages. We have determined by electron cryomicroscopy the structure of the vesicular stomatitis virus (VSV) L protein. The density map, at a resolution of 3.8 Å, has led to an atomic model for nearly all of the 2109-residue polypeptide chain, which comprises three enzymatic domains (RNA-dependent RNA polymerase [RdRp], polyribonucleotidyl transferase [PRNTase], and methyltransferase) and two structural domains. The RdRp resembles the corresponding enzymatic regions of dsRNA virus polymerases and influenza virus polymerase. A loop from the PRNTase (capping) domain projects into the catalytic site of the RdRp, where it appears to have the role of a priming loop and to couple product elongation to large-scale conformational changes in L.
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 20115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 20115, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA 20115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 20115, USA.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 20115, USA.
authors.forename: Simon
authors.initials: S
authors.lastname: Jenni
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 20115, USA.
authors.forename: Amal A
authors.initials: AA
authors.lastname: Rahmeh
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 20115, USA.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Morin
authors.affiliation: Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Grant
authors.affiliation: Howard Hughes Medical Institute, Janelia Research Campus, 19700 Helix Drive, Ashburn, VA 20147, USA.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Grigorieff
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 20115, USA; Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 20115, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Harrison
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 20115, USA. Electronic address: sean_whelan@hms.harvard.edu.
authors.forename: Sean P J
authors.initials: SPJ
authors.lastname: Whelan
mesh_terms: D020285:Cryoelectron Microscopy; D012321:DNA-Directed RNA Polymerases / Q000737:chemistry* / Q000648:ultrastructure*; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D014721:Vesicular stomatitis Indiana virus / Q000737:chemistry*; D014764:Viral Proteins / Q000737:chemistry* / Q000648:ultrastructure*
chemical_list: D014764:Viral Proteins; D012321:DNA-Directed RNA Polymerases; C512399:L polymerase protein, Vesicular stomatitis-Indiana virus