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

• Published in: Nature 2004-09, Vol.431 (7008), p.590-596
• Main Authors: Deuerling, Elke, Ban, Nenad, Ferbitz, Lars, Maier, Timm, Patzelt, Holger, Bukau, Bernd
• Format: Article
• Language: English
• Subjects: Analytical, structural and metabolic biochemistry; Bacteria; Biological and medical sciences; Biosynthesis; Brackish; Crystallization; Crystallography, X-Ray; E coli; Escherichia coli; Escherichia coli - metabolism; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Fundamental and applied biological sciences. Psychology; General aspects, investigation methods; Haloarcula marismortui; Humanities and Social Sciences; Hydrophobic and Hydrophilic Interactions; letter; Marine; Microbiology; Models, Genetic; Models, Molecular; Molecular biology; Molecular Chaperones - chemistry; Molecular Chaperones - metabolism; multidisciplinary; Peptidylprolyl Isomerase - chemistry; Peptidylprolyl Isomerase - metabolism; Protein Binding; Protein Biosynthesis; Protein Conformation; Protein Folding; Protein Subunits - chemistry; Protein Subunits - metabolism; Proteins; Proteins - chemistry; Proteins - metabolism; Ribonucleic acid; Ribosomes - chemistry; Ribosomes - metabolism; RNA; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature02899

During protein biosynthesis, nascent polypeptide chains that emerge from the ribosomal exit tunnel encounter ribosome-associated chaperones, which assist their folding to the native state. Here we present a 2.7 Å 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 peptidyl-prolyl 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.