Global Dynamics of a Protein on the Surface of Anisotropic Lipid Nanoparticles Derived from Relaxation-Based NMR Spectroscopy

The global motions of ubiquitin, a model protein, on the surface of aniso tro p ically tumbling 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1 '-rac-glycerol) (POPG):1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) bicelles are described. The shapes of POPG:DHPC bicelles prepared with high molar ratios q of POPG to DHPC can be approximated by prolate ellipsoids, with the ratio of ellipsoid dimensions and dimensions themselves increasing with higher values of q. Adaptation of the nuclear magnetic resonance (NMR) relaxation-based approach that we previously developed for interactions of ubiquitin with spherical POPG liposomes (Ceccon, A. et al. J. Am. Chem. Soc. 2016, 138, 5789-5792) allowed us to quantitatively analyze the variation in lifetime line broadening of NMR signals (Delta R-2) measured for ubiquitin in the presence of q = 2 POPG:DHPC bicelles and the associated transverse spin relaxation rates (R-2,B) of bicelle-bound ubiquitin. Ubiquitin, transiently bound to POPG:DHPC bicelles, undergoes internal rotation about an axis orthogonal to the surface of the bicelle and perpendicular to the principal axis of its rotational diffusion tensor on the low microsecond time scale (similar to 3 mu s), while the rotation axis itself wobbles in a cone on a submicrosecond time scale (<= 500 ns).

Automated summary

The global motions of ubiquitin on the surface of bicelles were studied. Ubiquitin undergoes internal rotation on the bicelle surface, while the rotation axis wobbles in a cone motion.