In the paper Proske*, Janowski" et al. the effects of several published genetic variations in the PURA gene have been assessed. The authors used recombinant protein expression, X-ray crystallography, NMR, and molecular dynamics simulations to study the fold integrity of PURA with patient-related mutations, Furthermore, the impact of such genetic variations on the proteins in vitro RNA binding and RNA unwinding as well as on their sub-cellular localization to processing bodies (P-bodies) was analyzed.
Proske, Janowski et al. show how molecular analysis of patient mutations can reveal the mechanisms of a disease at the cell level. The results show that the impact of mutations on the structural integrity of the protein, which affects its ability to bind RNA, is likely key to the symptoms of the syndrome. Additionally, their approach establishes a way to predict and test mutations that will cause PURA syndrome. This may help to develop diagnostic tools for this condition.
Further reading:
eLife digest:
https://elifesciences.org/digests/93561/finding-pura
eLife manuscript Proske*, Janowski* et al.:
https://elifesciences.org/articles/93561