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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.

SUBMITTER: Tang X

PROVIDER: S-EPMC4917968 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus.

Tang Xuhua X Zhu Yiping Y Baker Stacey L SL Bowler Matthew W MW Chen Benjamin Jieming BJ Chen Chen C Hogg J Robert JR Goff Stephen P SP Song Haiwei H

Nature communications 20160622

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 ...[more]

PMID: 27329342

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Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus.

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Structural basis of suppression of host translation termination by Moloney Murine Leukemia Virus.

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