Premium
Rescue of the neuroblastoma mutant of the human nucleoside diphosphate kinase A/nm23‐H1 by the natural osmolyte trimethylamine‐ N ‐oxide
Author(s) -
Georgescauld Florian,
Mocan Iulia,
Lacombe Marie-Lise,
Lascu Ioan
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.01.043
Subject(s) - trimethylamine n oxide , chemistry , osmolyte , denaturation (fissile materials) , urea , biochemistry , mutant , protein folding , folding (dsp implementation) , trimethylamine , protein subunit , point mutation , biophysics , biology , nuclear chemistry , electrical engineering , gene , engineering
The point mutation S120G in human nucleoside diphosphate kinase A, identified in patients with neuroblastoma, causes a protein folding defect. The urea‐unfolded protein cannot refold in vitro, and accumulates as a molten globule folding intermediate. We show here that the trimethylamine‐ N ‐oxide (TMAO) corrects the folding defect and stimulated subunit association. TMAO also substantially increased the stability to denaturation by urea of both wild‐type and S120G mutant. A non‐native folding intermediate accumulated in the presence of 4.5–7 M urea and of 2 M TMAO. It was inactive, monomeric, contained some secondary structure but no tertiary structure and displayed a remarkable stability to denaturation.