title: Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus.
abstract: Retroviral reverse transcriptase (RT) of Moloney murine leukemia virus (MoMLV) is expressed in the form of a large Gag-Pol precursor protein by suppression of translational termination in which the maximal efficiency of stop codon read-through depends on the interaction between MoMLV RT and peptidyl release factor 1 (eRF1). Here, we report the crystal structure of MoMLV RT in complex with eRF1. The MoMLV RT interacts with the C-terminal domain of eRF1 via its RNase H domain to sterically occlude the binding of peptidyl release factor 3 (eRF3) to eRF1. Promotion of read-through by MoMLV RNase H prevents nonsense-mediated mRNA decay (NMD) of mRNAs. Comparison of our structure with that of HIV RT explains why HIV RT cannot interact with eRF1. Our results provide a mechanistic view of how MoMLV manipulates the host translation termination machinery for the synthesis of its own proteins.
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
authors.forename: Xuhua
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, HHSC 1310C, 701 West 168th Street, New York, New York 10032, USA.|Howard Hughes Medical Institute, Columbia University, HHSC 1310C, 701 West 168th Street, New York, NY 10032, USA.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, Maryland 20892, USA.
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Baker
authors.affiliation: European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, Grenoble F-38042, France.|Unit of Virus Host-Cell Interactions, University Grenoble Alpes-EMBL-CNRS, 71 Avenue des Martyrs, CS 90181, Grenoble F-38042, France.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Bowler
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
authors.forename: Benjamin Jieming
authors.initials: BJ
authors.lastname: Chen
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, 50 South Drive, Bethesda, Maryland 20892, USA.
authors.forename: J Robert
authors.initials: JR
authors.lastname: Hogg
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, HHSC 1310C, 701 West 168th Street, New York, New York 10032, USA.|Howard Hughes Medical Institute, Columbia University, HHSC 1310C, 701 West 168th Street, New York, NY 10032, USA.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Goff
authors.affiliation: Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.|Life Sciences Institute, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, China.|Department of Biochemistry, National University of Singapore, 14 Science Drive, Singapore 117543, Singapore.
authors.forename: Haiwei
authors.initials: H
authors.lastname: Song
mesh_terms: D000818:Animals; D002151:Calorimetry; D018388:Codon, Terminator; D015685:Fusion Proteins, gag-pol / Q000378:metabolism; D057809:HEK293 Cells; D054303:HIV Reverse Transcriptase / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008979:Moloney murine leukemia virus / Q000378:metabolism*; D009154:Mutation; D059365:Nonsense Mediated mRNA Decay; D010443:Peptide Chain Termination, Translational; D010454:Peptide Termination Factors / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D012333:RNA, Messenger / Q000378:metabolism; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D016914:Ribonuclease H / Q000737:chemistry / Q000378:metabolism
chemical_list: D018388:Codon, Terminator; C489003:Etf1 protein, mouse; D015685:Fusion Proteins, gag-pol; D010454:Peptide Termination Factors; D012333:RNA, Messenger; C087971:peptide-chain-release factor 3; D054303:HIV Reverse Transcriptase; D012194:RNA-Directed DNA Polymerase; D016914:Ribonuclease H