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.
Price
W Nicholson
WN
Northeast Structural Genomics Consortium, Columbia University, New York, New York 10027, USA.
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
D000465:Algorithms; D000818:Animals; D001703:Biophysics / Q000379:methods; D019295:Computational Biology / Q000379:methods; D003460:Crystallization; D019277:Entropy; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D015233:Models, Statistical; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013499:Surface Properties; D013816:Thermodynamics
D000939:Epitopes; D011506:Proteins