title: Decoding Mammalian Ribosome-mRNA States by Translational GTPase Complexes.
abstract: In eukaryotes, accurate protein synthesis relies on a family of translational GTPases that pair with specific decoding factors to decipher the mRNA code on ribosomes. We present structures of the mammalian ribosome engaged with decoding factor⋅GTPase complexes representing intermediates of translation elongation (aminoacyl-tRNA⋅eEF1A), termination (eRF1⋅eRF3), and ribosome rescue (Pelota⋅Hbs1l). Comparative analyses reveal that each decoding factor exploits the plasticity of the ribosomal decoding center to differentially remodel ribosomal proteins and rRNA. This leads to varying degrees of large-scale ribosome movements and implies distinct mechanisms for communicating information from the decoding center to each GTPase. Additional structural snapshots of the translation termination pathway reveal the conformational changes that choreograph the accommodation of decoding factors into the peptidyl transferase center. Our results provide a structural framework for how different states of the mammalian ribosome are selectively recognized by the appropriate decoding factor⋅GTPase complex to ensure translational fidelity.
authors.affiliation: MRC-LMB, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Sichen
authors.initials: S
authors.lastname: Shao
authors.affiliation: MRC-LMB, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Jason
authors.initials: J
authors.lastname: Murray
authors.affiliation: MRC-LMB, Francis Crick Avenue, Cambridge CB2 0QH, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Brown
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jack
authors.initials: J
authors.lastname: Taunton
authors.affiliation: MRC-LMB, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: ramak@mrc-lmb.cam.ac.uk.
authors.forename: V
authors.initials: V
authors.lastname: Ramakrishnan
authors.affiliation: MRC-LMB, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: rhegde@mrc-lmb.cam.ac.uk.
authors.forename: Ramanujan S
authors.initials: RS
authors.lastname: Hegde
mesh_terms: D000818:Animals; D020285:Cryoelectron Microscopy; D004720:Endonucleases; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry*; D012270:Ribosomes / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D008840:Microfilament Proteins; D009687:Nuclear Proteins; D010445:Peptide Elongation Factors; D012333:RNA, Messenger; D004720:Endonucleases; C550527:pelo protein, human
keywords: cryo-EM; mRNA decoding; mammalian ribosome; protein translation; translational GTPase