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Title

Understanding the Physical Properties that Control Protein Crystallization by Analysis of LargeScale Experimental Data

Authors

W. Nicholson Price II, University of New Hampshire School of Law
Yang Chen, Northeast Structural Genomics Consortium, Columbia University
Samuel K. Handelman, Northeast Structural Genomics Consortium, Columbia University
Helen Neely, Northeast Structural Genomics Consortium, Columbia University
Philip Manor, Northeast Structural Genomics Consortium, Columbia UniversityFollow
Richard Karlin, Northeast Structural Genomics Consortium, Columbia University
Rajesh Nair, Northeast Structural Genomics Consortium, Columbia University
Jinfeng Liu, Northeast Structural Genomics Consortium, Columbia University
Michael Baran, Northeast Structural Genomics Consortium, Columbia University
John Everett, Northeast Structural Genomics Consortium, Columbia UniversityFollow
Saichiu N. Tong, Northeast Structural Genomics Consortium, Columbia University
Farhad Forouhar, Northeast Structural Genomics Consortium, Columbia University
Swarup S. Swaminathan, Northeast Structural Genomics Consortium, Columbia University
Thomas Acton, Northeast Structural Genomics Consortium, Columbia UniversityFollow
Rong Xiao, Northeast Structural Genomics Consortium, Columbia University
Joseph R. Luft, Northeast Structural Genomics Consortium, Columbia University
Angela Lauricella, Northeast Structural Genomics Consortium, Columbia University
George T. DeTitta, Northeast Structural Genomics Consortium, Columbia University
Burkhard Rost, Northeast Structural Genomics Consortium, Columbia UniversityFollow
Gaetano T. Montelione, Northeast Structural Genomics Consortium, Columbia University
John T. Hunt, Northeast Structural Genomics Consortium, Columbia University

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

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

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