Structural features and value of protein crystals grown in reduced gravity environments - An overview on investigations with APCF

Protein crystallisation experiments in reduced gravity environments have been conducted in a variety of set-ups. Here we are summarising the results of assays that were conducted with the Advanced Protein Crystallisation Facility (APCF) during six space missions that took place over more than a decade. We recall that the design of this facility is such that control experiments within APCF crystallisation cells can be run in parallel on earth. At first, we will shortly present the contribution of the APCF investigations to the physics of protein crystal growtha. The main goal, however, will be the critical analysis of the data from the viewpoint of crystal quality and structural biology. Doing so, we aim to bring an answer to the two following questions. (i) Is the quality of the crystals grown in reduced gravity superior to that of controls prepared on earth under otherwise identical conditions? (ii) Can more accurate three-dimensional structures be derived from the crystallographic analysis of space-grown crystals? Statistic analysis of the data strongly support the fact that microgravity has a positive effect on crystallisation and on crystal quality (about 52% of the crystals prepared in space diffracted X-rays to a higher resolution than any ground control crystal). Attempts to correlate the effect of microgravity with other physical chemical parameters remained unsuccessful. For instance, no apparent correlation could be established between the probability of success for microgravity and any system-dependent property such as the isoelectric point of the protein or the solvent content of the crystal. On the contrary, an anti-correlation was found with the protein molecular size. So far, the structure of 12 proteins crystallised in APCF has been determined at previously unachieved resolution. Practical implications for structural determination are emphasised and physical chemical theories explaining the effect of microgravity will be presented. Finally, recommendations are given for improving the performance of protein crystallisation experiments in microgravity and on earth.Reference: (a) Vergara et al., Acta Cryst., 59 (2003) 2.