title: Dynamic association of trigger factor with protein substrates.
abstract: Trigger factor is a ribosome-bound folding helper, which, apparently, combines two functions, chaperoning of nascent proteins and catalyzing prolyl isomerization in their folding. Immediate chaperone binding at the ribosome might interfere with rapid protein folding reactions, and we find that trigger factor indeed retards the in vitro folding of a protein with native prolyl isomers. The kinetic analysis of trigger factor binding to a refolding protein reveals that the adverse effects of trigger factor on conformational folding are minimized by rapid binding and release. The complex between trigger factor and a substrate protein is thus very short-lived, and fast-folding proteins can escape efficiently from an accidental interaction with trigger factor. Protein chains with incorrect prolyl isomers cannot complete folding and therefore can rebind for further rounds of catalysis. Unlike DnaK, trigger factor interacts with substrate proteins in a nucleotide-independent binding reaction, which seems to be optimized for high catalytic activity rather than for chaperone function. The synthetic lethality, observed when the genes for both DnaK and trigger factor are disrupted, might result from an indirect linkage. In the absence of trigger factor, folding is retarded and more aggregates form, which can neither be prevented nor disposed of when DnaK is lacking as well.
authors.affiliation: Laboratorium für Biochemie, Universität Bayreuth, D-95440 Bayreuth, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Maier
authors.forename: C
authors.initials: C
authors.lastname: Scholz
authors.forename: F X
authors.initials: FX
authors.lastname: Schmid
mesh_terms: D019943:Amino Acid Substitution; D001059:Apoproteins / Q000737:chemistry / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002942:Circular Dichroism; D002950:Citrate (si)-Synthase / Q000737:chemistry / Q000378:metabolism; D029968:Escherichia coli Proteins; D017353:Gene Deletion; D005804:Genes, Lethal / Q000235:genetics; D019791:Guanidine / Q000494:pharmacology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006207:Half-Life; D007536:Isomerism; D007700:Kinetics; D007768:Lactalbumin / Q000737:chemistry / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D019696:Peptidylprolyl Isomerase / Q000235:genetics / Q000378:metabolism*; D011392:Proline / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D011489:Protein Denaturation / Q000187:drug effects; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D006163:Ribonuclease T1 / Q000737:chemistry / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013816:Thermodynamics
chemical_list: D001059:Apoproteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D011506:Proteins; D007768:Lactalbumin; D011392:Proline; D002950:Citrate (si)-Synthase; D006163:Ribonuclease T1; C063842:dnaK protein, E coli; C403324:trigger factor, E coli; D019696:Peptidylprolyl Isomerase; D019791:Guanidine