Solvation of the folding-transition state in Pseudomonas aeruginosa azurin is modulated by metal: Solvation of azurin's folding nucleus

Protein Science : a Publication of the Protein Society
Corey J WilsonPernilla Wittung-Stafshede

Abstract

The role of water in protein folding, specifically its presence or not in the transition-state structure, is an unsolved question. There are two common classes of folding-transition states: diffuse transition states, in which almost all side chains have similar, rather low phi (phi) values, and polarized transition states, which instead display distinct substructures with very high phi-values. Apo-and zinc-forms of Pseudomonas aeruginosa azurin both fold in two-state equilibrium and kinetic reactions; while the apo-form exhibits a polarized transition state, the zinc form entails a diffuse, moving transition state. To examine the presence of water in these two types of folding-transition states, we probed the equilibrium and kinetic consequences of replacing core valines with isosteric threonines at six positions in azurin. In contrast to regular hydrophobic-to-alanine phi-value analysis, valine-to-threonine mutations do not disrupt the core packing but stabilize the unfolded state and can be used to assess the degree of solvation in the folding-transition state upon combination with regular phi-values. We find that the transition state for folding of apo-azurin appears completely dry, while that for zinc-azurin involves partia...Continue Reading

Citations

Nov 27, 2008·Proceedings of the National Academy of Sciences of the United States of America·Erik SedlákPernilla Wittung-Stafshede
Jan 8, 2010·Journal of Molecular Biology·Alice I Bartlett, Sheena E Radford
Aug 28, 2007·Archives of Biochemistry and Biophysics·Carla Mattos, A Clay Clark
Jul 11, 2013·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Stefania EvoliBruno Rizzuti
Jan 1, 2018·Quarterly Reviews of Biophysics·Candan Ariöz, Pernilla Wittung-Stafshede
Apr 6, 2021·The Journal of Physical Chemistry. B·Fabio C ZegarraMargaret S Cheung
Apr 10, 2019·The Journal of Physical Chemistry. B·Fabio C ZegarraMargaret S Cheung

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