Title: Structural basis for protein antiaggregation activity of the trigger factor chaperone
Authors: Saio, Tomohide ×
Guan, Xiao
Rossi, Paolo
Economou, Anastassios
Kalodimos, Charalampos G #
Issue Date: May-2014
Publisher: American Association for the Advancement of Science
Series Title: Science vol:344 issue:6184 pages:1250494
Article number: 10.1126/science.1250494
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.
ISSN: 0036-8075
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular Bacteriology (Rega Institute)
× corresponding author
# (joint) last author

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