Understanding the Physical Properties that Control Protein Crystallization by Analysis of Large-Scale Experimental Data
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.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States). National Synchrotron Light Source
- Sponsoring Organization:
- Doe - Office Of Science
- DOE Contract Number:
- DE-AC02-98CH10886
- OSTI ID:
- 980665
- Report Number(s):
- BNL-93583-2010-JA; NABIF9; TRN: US201015%%2050
- Journal Information:
- Nature Biotechnology, Vol. 27; ISSN 1087-0156
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
CONTROL
CORRELATIONS
CRYSTALLIZATION
DATA
DIFFRACTION METHODS
EXPERIMENTAL DATA
HUMAN POPULATIONS
INTERACTIONS
MINING
PHYSICAL PROPERTIES
PROBABILITY
PROTEIN STRUCTURE
PROTEINS
STABILITY
SUPPORTS
SURFACES
THERMODYNAMICS
national synchrotron light source