ProteoPlex: stability optimization of macromolecular complexes by sparse-matrix screening of chemical space
2015 | journal article. A publication with affiliation to the University of Göttingen.
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ProteoPlex: stability optimization of macromolecular complexes by sparse-matrix screening of chemical space
Chari, A.; Haselbach, D.; Kirves, J.-M.; Ohmer, J.; Paknia, E.; Fischer, N. & Ganichkin, O. et al. (2015)
Nature Methods, 12(9) pp. 859-865. DOI: https://doi.org/10.1038/nmeth.3493
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Details
- Authors
- Chari, Ashwin; Haselbach, David; Kirves, Jan-Martin; Ohmer, Juergen; Paknia, Elham; Fischer, Niels ; Ganichkin, Oleg; Frye, Jeremiah J.; Petzold, Georg; Jarvis, Marc; Tietzel, Michael; Grimm, Clemens; Peters, Jan-Michael; Schulman, Brenda A.; Tittmann, Kai ; Fischer, Utz; Stark, Holger ; Möller, Vanessa; Markl, Jürgen
- Abstract
- Molecular machines or macromolecular complexes are supramolecular assemblies of biomolecules with a variety of functions. Structure determination of these complexes in a purified state is often tedious owing to their compositional complexity and the associated relative structural instability. To improve the stability of macromolecular complexes in vitro, we present a generic method that optimizes the stability, homogeneity and solubility of macromolecular complexes by sparse-matrix screening of their thermal unfolding behavior in the presence of various buffers and small molecules. The method includes the automated analysis of thermal unfolding curves based on a biophysical unfolding model for complexes. We found that under stabilizing conditions, even large multicomponent complexes reveal an almost ideal two-state unfolding behavior. We envisage an improved biochemical understanding of purified macromolecules as well as a substantial boost in successful macromolecular complex structure determination by both X-ray crystallography and cryo-electron microscopy.
- Issue Date
- 2015
- Status
- published
- Publisher
- Nature Publishing Group
- Journal
- Nature Methods
- ISSN
- 1548-7091
- eISSN
- 1548-7105
- Language
- English