Novel approach to controlled protein crystallization through ligandation of yttrium cations

Zhang, Fajun; Zocher, Georg; Sauter, Andrea; Stehle, Thilo; Schreiber, Frank

doi:10.1107/s0021889811017997

Cited by 59 publications

(159 citation statements)

References 56 publications

(71 reference statements)

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“…This observation is also consistent with our previous study of the crystal structures that the BLG dimer is the building block of the crystal lattice. 28 ■ ASSOCIATED CONTENT…”

Section: ■ Conclusionmentioning

confidence: 99%

“…13°C (after 70 min), this correlation peak disappears completely. The crystallographic analysis in our previous work 28 indicates that the BLG dimer is the building block of the crystal lattice. Therefore, the The Journal of Physical Chemistry B Article temperature dependent monomer− monomer correlation peak may be related to the flexibility of proteins within the aggregates.…”

Section: ■ Introductionmentioning

confidence: 98%

“…The label of classical indicates that near c* crystallization takes place without visible precursor; the label of nonclassical indicates that close to c** aggregates or a dense liquid phase appear before crystallization as reported in a previous study. 28 The sticky hard sphere potential is used to describe the short-range attraction between protein clusters, which is defined by 48…”

Section: ■ Introductionmentioning

confidence: 99%

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Structural Evolution of Metastable Protein Aggregates in the Presence of Trivalent Salt Studied by (V)SANS and SAXS

et al. 2016

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We present a study of the structural evolution of protein aggregates formed in solutions of a globular protein, β-lactoglobulin (BLG), in the presence of YCl3. These aggregates are often observed before crystallization starts and they are metastable with respect to the crystalline phase. Here we focus on the characterization of the hierarchical structure of this intermediate phase and its temperature dependent structure evolution using a combination of (very) small angle neutron and X-ray scattering (VSANS, SANS, and SAXS). Results show that the hierarchical structure ranges from nanometer scale protein monomer, dimer and compact protein clusters to micrometer scale fractal protein aggregates. Upon cooling, the overall hierarchical structure is preserved, but the evolution of the internal structure within the aggregates is clearly visible: the monomer-monomer correlation peak reduces its intensity and disappears completely at lower temperatures, whereas the cluster-cluster correlation is enhanced. At a larger length scale, the fractal dimension of protein aggregates increases. The kinetics of the structure change during a temperature ramp was further investigated using time-resolved SAXS. The time dependent SAXS profiles show clear isosbestic points and the kinetics of the structural evolution can be well described using a two-state model. These dynamic properties of protein aggregates on a broad length scale may be essential for being the precursors of nucleation.

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“…This observation is also consistent with our previous study of the crystal structures that the BLG dimer is the building block of the crystal lattice. 28 ■ ASSOCIATED CONTENT…”

Section: ■ Conclusionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 98%

Section: ■ Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Structural Evolution of Metastable Protein Aggregates in the Presence of Trivalent Salt Studied by (V)SANS and SAXS

et al. 2016

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“…Such a transformation may be possible for real proteins by adjusting solvent chemistry. For instance, recent experiments suggest that increasing multivalent salt concentration can facilitate protein crystal assembly by inducing specific contacts between proteins [43].…”

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confidence: 99%

Design rules for the self-assembly of a protein crystal

Haxton

Whitelam

2012

Soft Matter

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Theories of protein crystallization based on spheres that form close-packed crystals predict optimal assembly within a 'slot' of second virial coefficients and enhanced assembly near the metastable liquid-vapor critical point. However, most protein crystals are open structures stabilized by anisotropic interactions. Here, we use theory and simulation to show that assembly of one such structure is not predicted by the second virial coefficient or enhanced by the critical point. Instead, good assembly requires that the thermodynamic driving force be on the order of the thermal energy and that interactions be made as nonspecific as possible without promoting liquid-vapor phase separation.The need to crystallize proteins for X-ray studies has spurred the development of theories of protein crystallization. These theories are largely based on the behavior of spheres with short-range isotropic attractions, a representation motivated by two observations. First, phase diagrams for typical proteins and spherical colloids with short range attractions are structurally similar, possessing a metastable demixing transition between a vapor of solute (solute-poor solution) and a liquid of solute (solute-rich solution) [1][2][3][4]. Second, both proteins and spherical colloids tend to crystallize when the second virial coefficient, an orientationally-averaged measure of protein-protein attraction, lies in a defined 'crystallization slot ' [5-7]. On the computer, short-range isotropic spheres crystallize poorly above the metastable liquidvapor binodal and show enhanced nucleation rates near or below it [3,[8][9][10][11][12]. Such enhancement is indeed seen in some protein solutions [13][14][15]. However, other experiments show disparities with this picture. Proteins can crystallize readily above the binodal [16,17] and experience kinetically-impaired crystallization below it [18]. They can also lie in the crystallization slot and not crystallize [19]. In addition, although the structure of protein and colloid phase diagrams is similar, the microscopic nature of the stable solid is not: most proteins do not form close-packed crystals [20].These disparities motivate a theoretical approach to protein crystallization that acknowledges additional features of proteins' interactions, particularly their anisotropy [21][22][23][24][25][26]. Such studies suggest that rules for optimal assembly of open structures are different from the rules for optimal assembly of close-packed structures. Here we explicitly demonstrate this difference. We have used extensive equilibrium and nonequilibrium numerical simulations and quantitatively accurate mean-field theory to exhaustively determine the design rules for optimal assembly of a model patterned after the SbpA surface-layer protein. The latter forms a porous square lattice with a tetrameric repeat unit on the surface of the bacterium Lysinibacillus sphaericus, and in vitro on surfaces or in solution [27][28][29][30]. We impose a simple set of model protein interactions that stabilize the two conde...

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“…This anomalous trend, caused by charge reversal, has been shown to be able to induce clustering, liquid-liquid phase separation or crystallization. 12,18,[21][22][23][24][25] The ability to control the phase behavior of protein dispersions show promising opportunities, for example for the production of high quality protein crystals, required for protein structure determination.…”

Section: Introductionmentioning

confidence: 99%

Anomalous Protein–Protein Interactions in Multivalent Salt Solution

et al. 2017

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1 AbstractThe stability of aqueous protein solutions is strongly affected by multivalent ions, which induce ion-ion correlations beyond the scope of classical mean-field theory. Using all-atom Molecular Dynamics (MD) and coarse grained Monte Carlo (MC) simulations, we investigate the interaction between a pair of protein molecules in 3:1 electrolyte solution. In agreement with available experimental findings of "reentrant protein condensation", we observe an anomalous trend in the protein-protein potential of mean force with increasing electrolyte concentration in the order: (i) double-layer repulsion,(ii) ion-ion correlation attraction, (iii) over-charge repulsion, and in excess of 1:1 salt, (iv) non Coulombic attraction. To efficiently sample configurational space we explore hybrid continuum solvent models, applicable to many-protein systems, where weakly coupled ions are treated implicitly, while strongly coupled ones are treated explicitly.Good agreement is found with the primitive model of electrolytes, as well as with atomic models of protein and solvent.2

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Novel approach to controlled protein crystallization through ligandation of yttrium cations

Cited by 59 publications

References 56 publications

Structural Evolution of Metastable Protein Aggregates in the Presence of Trivalent Salt Studied by (V)SANS and SAXS

Structural Evolution of Metastable Protein Aggregates in the Presence of Trivalent Salt Studied by (V)SANS and SAXS

Design rules for the self-assembly of a protein crystal

Anomalous Protein–Protein Interactions in Multivalent Salt Solution

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