2MLX

NMR structure of E. coli Trigger Factor in complex with unfolded PhoA220-310

Summary for 2MLX

• Entry DOI: 10.2210/pdb2mlx/pdb
• Related: 2mly 2mlz
• NMR Information: BMRB: 19835
• Descriptor: Trigger factor, Alkaline phosphatase (2 entities in total)
• Functional Keywords: molecular chaperone, unfolded protein, protein complex, chaperone
• Biological source: Escherichia coli; More
• Cellular location: Cytoplasm: U6N3P1
• Total number of polymer chains: 2
• Total formula weight: 59562.24

Authors

Saio, T.,Guan, X.,Rossi, P.,Economou, A.,Kalodimos, C.G. (deposition date: 2014-03-05, release date: 2014-05-21, Last modification date: 2024-05-01)

Primary citation

Saio, T.,Guan, X.,Rossi, P.,Economou, A.,Kalodimos, C.G.
Structural basis for protein antiaggregation activity of the trigger factor chaperone.
Science, 344:1250494-1250494, 2014

PubMed 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.

PubMed: 24812405
DOI: 10.1126/science.1250494

Experimental method

SOLUTION NMR