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Genetic selection designed to stabilize proteins uncovers a chaperone called Spy
Author(s): Shu Quan, Philipp Koldewey, Tim Tapley, Nadine Kirsch, Karen M. Ruane, Jennifer Pfizenmaier, Rong Shi, Stephan Hofmann, Linda Foit, Guoping Ren, Ursula Jakob, Zhaohui Xu, Miroslaw Cygler, James C. A. Bardwell
To optimize the in vivo folding of proteins, James Bardwell and his research group linked protein stability to antibiotic resistance, thereby forcing bacteria to effectively fold and stabilize proteins. When they challenged Escherichia coli to stabilize a very unstable periplasmic protein, it massively overproduced a periplasmic protein called Spy, which increases the steady-state levels of a set of unstable protein mutants up to 700-fold. In vitro studies demonstrate that the Spy protein is an effective ATP-independent chaperone that suppresses protein aggregation and aids protein refolding. The research group's strategy opens up new routes for chaperone discovery and the custom tailoring of the in vivo folding environment. Spy forms thin, apparently flexible cradle-shaped dimers. The structure of Spy is unlike that of any previously solved chaperone, making it the prototypical member of a new class of small chaperones that facilitate protein refolding in the absence of energy cofactors.
Name of Periodical: Nature: Structural & Molecular Biology
Issue Number: 18
Year of Publication: 2011