Dr. Fajun Zhang "Tuning Interactions in Protein Solutions towards to Controlled Protein Crystallization"
Institut fuer Angewandte Physik, Universitaet Tuebingen
What |
|
---|---|
When |
Apr 12, 2011 from 02:15 PM to 03:00 PM |
Where | “Hörsaal Makromolekulare Chemie”, Stefan-Meier-Str. 31, Freiburg |
Add event to calendar |
vCal iCal |
Fajun Zhang, Marcell Wolf, Felix Roogen-Runge, Maximilian W. A. Skoda, Robert M. J. Jacobs, and Frank Schreiber
Abstract
Non-specific protein-protein interactions in aqueous solution play a crucial role on protein crystallization and the protein-aggregation related diseases, such as cataracts, and sickle cell anemia. The challenge of a comprehensive understanding is to tune and control the phase behavior in protein solutions. We have studied the phase behavior of model globular proteins in solution in the presence of multivalent counterions. It has been shown that negatively charged globular proteins at neutral pH in the presence of multivalent counterions undergo a “reentrant condensation (RC)” phase behavior [1,2], i.e. a phase-separated regime occurs in between two critical salt concentrations, c* < c**, giving a meta-stable liquid-liquid phase separation (LLPS). This reentrant phase behavior corresponds to an effective charge inversion of proteins as confirmed by zeta-potential measurements and supported by Monte Carlo simulations [1,2]. Crystallization from the condensed regime follows different mechanisms. Close to c*, crystals grow following a classic nucleation and growth mechanism; close to c**, the crystallization follows a two-step mechanism, i.e, crystals growth follows a meta-stable LLPS [3]. X-ray diffraction analyses on the high quality single crystals provide direct evidence of the crystal structure and cation binding sites [3]. Our discovery of the RC and LLPS induced by multivalent metal ions provides a new way to tune protein interactions with predictable phase behavior as well as controlling protein crystallization.
[1] Zhang, F.; Skoda, M. W. A.; Jacobs, R. M. J.; Zorn, S.; Martin, R. A.; Martin, C. M.; Clark, G. F.; Weggler, S.; Hildebrandt, A.; Kohlbacher, O.; Schreiber, F. Phys. Rev. Lett. 2008, 101, 148101.
[2] Zhang, F.; Weggler, S.; Ziller, M.; Ianeselli, L.; Heck, B. S.; Hildebrandt, A.; Kohlbacher, O.; Skoda, M. W. A.; Jacobs, R. M. J.; Schreiber, F. Proteins: Structure, Function, and Bioinformatics 2010, 78, 3450-3457.
[3] Zhang, F., Zocher, G., Sauter, A., Stehle, T. & Schreiber, F. J. Appl. Cryst. 2011 Accepted.