La Jolla, LA, March 30, 2021 – Litao Sun, et al, at Scripps Research used the switchSENSE® technology in their paper to analyze the different conformations of the wild-type and mutant versions of the alanyl-tRNA synthetase protein (AlaRS).
The switchSENSE conformation analysis robustly detected four mutations in AlaRS leading to up to 12% size increase over the wild-type as major drivers of #tRNA synthetase expansion. These results were confirmed by further independent biophysical analyses (small-angle X-ray scattering and hydrogendeuterium exchange). Interestingly, an expansion of the protein by mutations in the aminoacylation domain was shown to correlate with increased neuropilin 1 (Nrp 1) binding capabilities and disease severity of the Charcot-Marie-Tooth disease, a neurological disorder.
With this finding, the conformation analysis helped to understand the connection between AlaRS expansion and Nrp binding, thus providing more insights to potentially cure this inherited disorder.