Analysis abstract
Nature Biotechnology 27, 51 - 57 (2008)
Published online: 14 December 2008 | doi:10.1038/nbt.1514
Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data
W Nicholson Price II1,2, Yang Chen1,2, Samuel K Handelman1,2, Helen Neely1,2, Philip Manor1,2, Richard Karlin1,2, Rajesh Nair1,3, Jinfeng Liu1,3, Michael Baran1,4, John Everett1,4, Saichiu N Tong1,4, Farhad Forouhar1,2, Swarup S Swaminathan1,2, Thomas Acton1,4, Rong Xiao1,4, Joseph R Luft1,5, Angela Lauricella1,5, George T DeTitta1,5, Burkhard Rost1,3, Gaetano T Montelione1,4,6 & John F Hunt1,2
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.
- Northeast Structural Genomics Consortium, 702A Fairchild Center, MC2434, Columbia University, New York, New York 10027, USA.
- Department of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, New York 10027, USA.
- Department of Biochemistry and Molecular Biophysics, Columbia University, New York, New York 10032, USA.
- Department of Molecular Biology and Biochemistry, Center for Advanced Biotechnology and Medicine, Rutgers University, Piscataway, New Jersey 08854, USA.
- Hauptman-Woodward Institute, 700 Ellicott Street, Buffalo, New York 14203, USA.
- Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854, USA.
Correspondence to: John F Hunt1,2 e-mail: jfhunt@biology.columbia.edu
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