title: Molecular mechanism and structure of Trigger Factor bound to the translating ribosome.
abstract: Ribosome-associated chaperone Trigger Factor (TF) initiates folding of newly synthesized proteins in bacteria. Here, we pinpoint by site-specific crosslinking the sequence of molecular interactions of Escherichia coli TF and nascent chains during translation. Furthermore, we provide the first full-length structure of TF associated with ribosome-nascent chain complexes by using cryo-electron microscopy. In its active state, TF arches over the ribosomal exit tunnel accepting nascent chains in a protective void. The growing nascent chain initially follows a predefined path through the entire interior of TF in an unfolded conformation, and even after folding into a domain it remains accommodated inside the protective cavity of ribosome-bound TF. The adaptability to accept nascent chains of different length and folding states may explain how TF is able to assist co-translational folding of all kinds of nascent polypeptides during ongoing synthesis. Moreover, we suggest a model of how TF's chaperoning function can be coordinated with the co-translational processing and membrane targeting of nascent polypeptides by other ribosome-associated factors.
authors.affiliation: Zentrum für Molekulare Biologie Heidelberg, DKFZ-ZMBH Alliance, Universität Heidelberg, Heidelberg, Germany.
authors.forename: Frieder
authors.initials: F
authors.lastname: Merz
authors.forename: Daniel
authors.initials: D
authors.lastname: Boehringer
authors.forename: Christiane
authors.initials: C
authors.lastname: Schaffitzel
authors.forename: Steffen
authors.initials: S
authors.lastname: Preissler
authors.forename: Anja
authors.initials: A
authors.lastname: Hoffmann
authors.forename: Timm
authors.initials: T
authors.lastname: Maier
authors.forename: Anna
authors.initials: A
authors.lastname: Rutkowska
authors.forename: Jasmin
authors.initials: J
authors.lastname: Lozza
authors.forename: Nenad
authors.initials: N
authors.lastname: Ban
authors.forename: Bernd
authors.initials: B
authors.lastname: Bukau
authors.forename: Elke
authors.initials: E
authors.lastname: Deuerling
mesh_terms: D000595:Amino Acid Sequence; D003432:Cross-Linking Reagents / Q000737:chemistry; D020285:Cryoelectron Microscopy; D029968:Escherichia coli Proteins / Q000737:chemistry*; D018832:Molecular Chaperones / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D019696:Peptidylprolyl Isomerase / Q000737:chemistry*; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D010455:Peptides; C403324:trigger factor, E coli; D019696:Peptidylprolyl Isomerase