by Peter Nollert
June 15, 2010 14:00
What would you give if you knew how the crystallizability of your target protein compares to 'what's our there'? There's a lot of talk about stability, crystallizability and their relationship and there are these hand waving arguments about supposedly problematic 'floppy regions' in proteins.
So here's a relevant paper that sheds solid data on this topic:
Price W.N. et al., Understanding the physical properties controlling protein crystallization based on analysis of large-scale experimental data. Nature Biotechnology 27(1), 51-57. 2009
The authors thoroughly mined crystallization data from NESG (Northeast Structural Genomics Consortium) and, amongst a lot of other interesting results, present evidence for these key findings:
1. Overall thermodynamic stability (thermal melt) is not a good predictor of crystallization success
But here's the good news as well: Higher crystallization propensity is found for:
2. Proteins that form defined dimers and higher-mers (as opposed to monomers or aggregated protein)
We DLS lovers always knew this, of course ;)
I was not satisfied though with this hyperbole that the paper concluded with: "The dominant factor determining protein crystallization outcome is the prevalence of well-ordered surface epitopes capable of mediating stereochemically specific interprotein packing interactions" - to me this sounds like: "if the molecules pack well with each other, they'll form crystals".
Duh - "The dominant factor determining protein crystallization outcome is the prevalence of well-ordered surface epitopes capable of mediating stereochemically specific interprotein packing interactions."
Nevertheless, their notion that Glycine, Alanine and Phenylalanine residues are 'good' for crystallization may serve as a useful guide when designing protein surface mutations to enhance your targets' crystallizability. Methinks that this will form a centerpiece in CAPCE (computer aided protein crystal engineering).
Cheers,
Peter