title: Dynamic enzyme docking to the ribosome coordinates N-terminal processing with polypeptide folding.
abstract: Newly synthesized polypeptides undergo various cotranslational maturation steps, including N-terminal enzymatic processing, chaperone-assisted folding and membrane targeting, but the spatial and temporal coordination of these steps is unclear. We show that Escherichia coli methionine aminopeptidase (MAP) associates with ribosomes through a charged loop that is crucial for nascent-chain processing and cell viability. MAP competes with peptide deformylase (PDF), the first enzyme to act on nascent chains, for binding sites at the ribosomal tunnel exit. PDF has extremely fast association and dissociation kinetics, which allows it to frequently sample ribosomes and ensure the processing of nascent chains after their emergence. Premature recruitment of the chaperone trigger factor, or polypeptide folding, negatively affect processing efficiency. Thus, the fast ribosome association kinetics of PDF and MAP are crucial for the temporal separation of nascent-chain processing from later maturation events, including chaperone recruitment and folding.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, Germany.
authors.forename: Arzu
authors.initials: A
authors.lastname: Sandikci
authors.forename: Felix
authors.initials: F
authors.lastname: Gloge
authors.forename: Michael
authors.initials: M
authors.lastname: Martinez
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Mayer
authors.forename: Rebecca
authors.initials: R
authors.lastname: Wade
authors.forename: Bernd
authors.initials: B
authors.lastname: Bukau
authors.forename: Günter
authors.initials: G
authors.lastname: Kramer
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D000595:Amino Acid Sequence; D017124:Conserved Sequence; D029968:Escherichia coli Proteins / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D025941:Protein Interaction Mapping; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012269:Ribosomal Proteins / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D029968:Escherichia coli Proteins; C512346:Map protein, E coli; D012269:Ribosomal Proteins; C032493:ribosomal protein L17; D000581:Amidohydrolases; C084507:peptide deformylase