Protein stabilizer, NDSB-195, enhances the dynamics of the β4-α2 loop of ubiquitin

July 28, 2017

Title

Protein stabilizer, NDSB-195, enhances the dynamics of the β4-α2 loop of ubiquitin

Author

Haimei Wang, Kazuo Hosoda, Takeshi Ishii, Ryo Arai, Toshiyuki Kohno, Shin-ichi Terawaki, Kaori Wakamatsu

Year

2016

Journal

Journal of Peptide Science

Abstract

Non-detergent sulfobetaines (NDSBs) are a new group of small, synthetic protein stabilizers, which have advantages over classical compatible osmolytes, such as polyol, amines, and amino acids: they do not increase solution viscosity, unlike polyols, and they are zwitterionic at all pH ranges, unlike amines and amino acids. NDSBs also facilitate the crystallization and refolding of proteins. The mechanism whereby NDSBs exhibit such activities, however, remains elusive. To gain insight into this mechanism, we studied, using nuclear magnetic resonance (NMR), the effects of dimethylethylammonium propane sulfonate (NDSB-195) on the dynamics of ubiquitin, on which a wealth of information has been accumulated. By analyzing the line width of amide proton resonances and the transverse relaxation rates of nitrogen atoms, we found that NDSB-195 enhances the microsecond–millisecond dynamics of a β4-α2 loop of ubiquitin. Although those compounds that enhance protein dynamics are generally considered to destabilize protein molecules, NDSB-195 enhanced the stability of ubiquitin against guanidium chloride denaturation. Thus, the simultaneous enhancement of stability and flexibility by a single compound can be attained.

Instrument

J-820

Keywords

Circular dichroism, Thermodynamics, Protein denaturation, Protein folding, Secondary structure, Biochemistry