Understanding the Physical Properties that Control Protein Crystallization by Analysis of LargeScale Experimental Data
Abstract
Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of entire predicted proteomes demonstrate substantial differences in the amino acid-sequence properties of human versus eubacterial proteins, which likely reflect differences in biophysical properties, including crystallization propensity. Our thermodynamic measurements do not generally support previous claims regarding correlations between sequence properties and protein stability.
Publication Date
1-1-2009
Journal Title
Nature Biotechnology
Digital Object Identifier (DOI)
doi:10.1038/nbt.1514
Document Type
Article
Recommended Citation
W. Nicholson Price II, "Understanding the Physical Properties that Control Protein Crystallization by Analysis of LargeScale Experimental Data," 27 NATURE BIOTECHNOLOGY 51 (2009) (with Yang Chen et al.) available at http://www.nature.com/nbt/journal/v27/n1/full/nbt.1514.html
Additional Information
Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746436/ and http://www.nature.com/nbt/journal/v27/n1/full/nbt.1514.html