Solution structure and dynamics of mouse ARMET

Abstract 

ARMET is an endoplasmic reticulum (ER) stress-inducible protein that is required for maintaining cell viability under ER stress conditions. However, the exact molecular mechanisms by which ARMET protects cells are unknown. Here, we have analyzed the solution structure of ARMET. ARMET has an entirely α-helical structure, which is composed of two distinct domains. Positive charges are dispersed on the surfaces of both domains and across a linker structure. Trypsin digestion and ¹⁵N relaxation experiments indicate that the tumbling of the N-terminal and C-terminal domains is effectively independent. These results suggest that ARMET may hold a negatively charged molecule using the two positively charged domains.

Abbreviations: ARMET, Arginine rich, mutated in early stage of tumors, DSS, 2,2-dimethyl-2-silapentane-5-sulfonic acid, bHLH, basic-helix–loop–helix, ER, endoplasmic reticulum, ERAD, ER-associated degradation, ERQC, ER quality control, HSQC, heteronuclear single quantum coherence, NOE, nuclear Overhauser effect, NOESY, nuclear Overhauser enhancement spectroscopy, RMSD, root-mean-square deviation, TOCSY, total correlated spectroscopy, UPR, unfolded protein response

Keywords: ER stress, Solution structure, Positive charge, Domain movement