Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins

During protein biosynthesis, nascent polypeptide chains that emerge from the ribosomal exit tunnel encounter ribosomeassociated chaperones, which assist their folding to the native state. Here we present a 2.7A ° crystal structure of Escherichia coli trigger factor, the best-characterized chaperone of this type, together with the structure of its ribosome-binding domain in complex with the Haloarcula marismortui large ribosomal subunit. Trigger factor adopts a unique conformation resembling a crouching dragon with separated domains forming the amino-terminal ribosome-binding tail , the peptidylprolyl isomerase head , the carboxy-terminal arms and connecting regions building up the back . From its attachment point on the ribosome, trigger factor projects the extended domains over the exit of the ribosomal tunnel, creating a protected folding space where nascent polypeptides may be shielded from proteases and aggregation. This study sheds new light on our understanding of co-translational protein folding, and suggests an unexpected mechanism of action for ribosome-associated chaperones