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Understanding the physical properties that control protein crystallization by analysis of large-scale 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.

SUBMITTER: Price WN

PROVIDER: S-EPMC2746436 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data.

Price W Nicholson WN Chen Yang Y Handelman Samuel K SK Neely Helen H Manor Philip P Karlin Richard R Nair Rajesh R Liu Jinfeng J Baran Michael M Everett John J Tong Saichiu N SN Forouhar Farhad F Swaminathan Swarup S SS Acton Thomas T Xiao Rong R Luft Joseph R JR Lauricella Angela A DeTitta George T GT Rost Burkhard B Montelione Gaetano T GT Hunt John F JF

Nature biotechnology 20090101 1

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 m ...[more]

PMID: 19079241

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Dataset Information

Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data.

Publications

Understanding the physical properties that control protein crystallization by analysis of large-scale experimental data.

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