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Significant new findings on protein folding dynamics
August 2012. The Faculty of 1000 has recommended recently published research by an international team lead by CEF speaker Harald Schwalbe as being of special significance in its field. The recommended study investigated the modulation of structure and dynamics by disulfide bond formation. During oxidative folding, the formation of disulfide bonds has profound effects on guiding the protein folding pathway. Comparatively little was known about the changes in the conformational dynamics in folding intermediates of proteins that contain only a subset of their native disulfide bonds. The comprehensive study by this international collaboration with universities from Japan, England and France (full affiliations) has now shed light on these dynamics by probing the conformational landscape of non-native states of lysozyme containing a single native disulfide bond utilizing nuclear magnetic resonance (NMR) spectroscopy, small-angle X-ray scattering (SAXS), circular dichroism (CD) data as well as modeling approaches. The results show that the impact on conformational dynamics varies widely depending on the loop size of the single disulfide variants and deviates significantly from random coil predictions for both NMR and SAXS data. From these experiments, the team concludes that the introduction of single disulfides spanning a large portion of the polypeptide chain shifts the structure and dynamics of hydrophobic core residues of the protein so that these regions exhibit levels of order comparable to the native state on the nanosecond time scale.
Link to F1000 recommendation
Link to research paper
Contact
Prof. Dr. Harald Schwalbe
Institut für Organische Chemie und Chemische Biologie Goethe-Universität Frankfurt
N160/R314
Max-von-Laue-Str. 7
60438 Frankfurt am Main
Telefon: +49 (0)69 798-29737
Fax: +49 (0)69 798-29515
Email: schwalbe@nmr.uni-frankfurt.de
schwalbe.org.chemie.uni-frankfurt.de
Full reference:
Silvers R, Sziegat F, Tachibana H, Segawa S, Whittaker S, Gunther UL, Gabel F, Huang JR, Blackledge M, Wirmer-Bartoschek J, Schwalbe H (2012) Modulation of Structure and Dynamics by Disulfide Bond Formation in Unfolded States. J Am Chem Soc 134:6846-6854.