Tartrate Chirality Determines Thaumatin Crystal Habit

A major challenge in structural biology is to produce high-quality protein crystals for X-ray diffraction. Currently, proteins are crystallized by trial and error, often in multicomponent solutions with chiral precipitants. As proteins are chiral molecules, we hypothesized that the chirality of the precipitants may affect crystallogenesis. To test this hypothesis, we crystallized thaumatin, an intensely sweet globular protein, with the three stereoisomers (l-, d-, and meso-) of tartaric acid. We find three different crystal habits and crystal packings; the three stereoisomers interact with the protein at different sites. All three precipitants produce high-quality crystals from which atomic resolution (∼1 Å) structures were obtained. Our findings suggest that stereospecific interactions with precipitants are important in protein crystal formation and should be controlled when crystallizing proteins for structure determination.