Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data
| Autor: | W. Nicholson Price, Gaetano T. Montelione, Swarup S Swaminathan, Thomas Acton, Saichiu N Tong, Farhad Forouhar, Jinfeng Liu, Burkhard Rost, Yang Chen, John F. Hunt, Joseph R. Luft, George T. DeTitta, Rajesh Nair, John K. Everett, Angela Lauricella, Philip C. Manor, Rong Xiao, Samuel K. Handelman, Richard Karlin, Michael Baran, Helen Neely |
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| Rok vydání: | 2008 |
| Předmět: |
Protein Folding
Surface Properties Entropy Biomedical Engineering Biophysics Bioengineering Computational biology Bioinformatics Applied Microbiology and Biotechnology Article law.invention Structural genomics Epitopes Protein stability Protein structure law Animals Humans Crystallization Models Statistical Chemistry Experimental data Computational Biology Proteins Proteome Molecular Medicine Thermodynamics Protein folding Protein crystallization Algorithms Biotechnology |
| Zdroj: | Nature biotechnology. 27(1) |
| ISSN: | 1546-1696 |
| Popis: | Crystallization has proven to be the most significant bottleneck to high-throughput protein structure determination using diffraction methods. We have used the large-scale, systematically generated experimental results of the Northeast Structural Genomics Consortium to characterize the biophysical properties that control protein crystallization. Datamining of crystallization results combined with explicit folding studies lead to the conclusion that crystallization propensity is controlled primarily by the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. These analyses identify specific sequence features correlating with crystallization propensity that can be used to estimate the crystallization probability of a given construct. Analyses of entire predicted proteomes demonstrate substantial differences in the bulk amino acid sequence properties of human versus eubacterial proteins that reflect likely differences in their biophysical properties including crystallization propensity. Finally, our thermodynamic measurements enable critical evaluation of previous claims regarding correlations between protein stability and bulk sequence properties, which generally are not supported by our dataset. |
| Databáze: | OpenAIRE |
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