Molecular mechanism and structure of Trigger Factor bound to the translating ribosome.
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.
Merz
Frieder
F
Zentrum für Molekulare Biologie Heidelberg, DKFZ-ZMBH Alliance, Universität Heidelberg, Heidelberg, Germany.
Boehringer
Daniel
D
Schaffitzel
Christiane
C
Preissler
Steffen
S
Hoffmann
Anja
A
Maier
Timm
T
Rutkowska
Anna
A
Lozza
Jasmin
J
Ban
Nenad
N
Bukau
Bernd
B
Deuerling
Elke
E
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*
D003432:Cross-Linking Reagents; D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D010455:Peptides; C403324:trigger factor, E coli; D019696:Peptidylprolyl Isomerase