title: Trigger factor in complex with the ribosome forms a molecular cradle for nascent proteins.
abstract: 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 A 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.
authors.affiliation: Institut für Molekularbiologie und Biophysik, Eidgenössische Technische Hochschule Hönggerberg (ETH Zürich), HPK Gebäude, CH-8093 Zürich, Switzerland.
authors.forename: Lars
authors.initials: L
authors.lastname: Ferbitz
authors.forename: Timm
authors.initials: T
authors.lastname: Maier
authors.forename: Holger
authors.initials: H
authors.lastname: Patzelt
authors.forename: Bernd
authors.initials: B
authors.lastname: Bukau
authors.forename: Elke
authors.initials: E
authors.lastname: Deuerling
authors.forename: Nenad
authors.initials: N
authors.lastname: Ban
mesh_terms: D003460:Crystallization; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000378:metabolism*; D019614:Haloarcula marismortui; D057927:Hydrophobic and Hydrophilic Interactions; D008957:Models, Genetic; D008958:Models, Molecular; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D014176:Protein Biosynthesis; D011487:Protein Conformation; D017510:Protein Folding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D029968:Escherichia coli Proteins; D018832:Molecular Chaperones; D021122:Protein Subunits; D011506:Proteins; C403324:trigger factor, E coli; D019696:Peptidylprolyl Isomerase