title: Structural basis for protein antiaggregation activity of the trigger factor chaperone.
abstract: Molecular chaperones prevent aggregation and misfolding of proteins, but scarcity of structural data has impeded an understanding of the recognition and antiaggregation mechanisms. We report the solution structure, dynamics, and energetics of three trigger factor (TF) chaperone molecules in complex with alkaline phosphatase (PhoA) captured in the unfolded state. Our data show that TF uses multiple sites to bind to several regions of the PhoA substrate protein primarily through hydrophobic contacts. Nuclear magnetic resonance (NMR) relaxation experiments show that TF interacts with PhoA in a highly dynamic fashion, but as the number and length of the PhoA regions engaged by TF increase, a more stable complex gradually emerges. Multivalent binding keeps the substrate protein in an extended, unfolded conformation. The results show how molecular chaperones recognize unfolded polypeptides and, by acting as unfoldases and holdases, prevent the aggregation and premature (mis)folding of unfolded proteins.
authors.affiliation: Center for Integrative Proteomics Research and Department of Chemistry and Chemical Biology, Rutgers University, Piscataway, NJ 08854, USA.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Saio
authors.forename: Xiao
authors.initials: X
authors.lastname: Guan
authors.forename: Paolo
authors.initials: P
authors.lastname: Rossi
authors.forename: Anastassios
authors.initials: A
authors.lastname: Economou
authors.forename: Charalampos G
authors.initials: CG
authors.lastname: Kalodimos
mesh_terms: D000469:Alkaline Phosphatase / Q000737:chemistry*; D001665:Binding Sites; D029968:Escherichia coli Proteins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D064267:Intrinsically Disordered Proteins / Q000737:chemistry*; D018832:Molecular Chaperones / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000737:chemistry; D019696:Peptidylprolyl Isomerase / Q000737:chemistry*; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D029968:Escherichia coli Proteins; D064267:Intrinsically Disordered Proteins; D018832:Molecular Chaperones; D010455:Peptides; D000469:Alkaline Phosphatase; C114089:phoA protein, E coli; D019696:Peptidylprolyl Isomerase