RT Journal Article
SR Electronic
T1 Slow conformational exchange and overall rocking motion in ubiquitin protein crystals
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 126813
DO 10.1101/126813
A1 Vilius Kurauskas
A1 Sergei A. Izmailov
A1 Olga N. Rogacheva
A1 Audrey Hessel
A1 Isabel Ayala
A1 Joyce Woodhouse
A1 Anastasya Shilova
A1 Yi Xue
A1 Tairan Yuwen
A1 Nicolas Coquelle
A1 Jacques-Philippe Colletier
A1 Nikolai R. Skrynnikov
A1 Paul Schanda
YR 2017
UL http://biorxiv.org/content/early/2017/04/12/126813.abstract
AB Proteins perform their functions in solution but their structures are most frequently studied inside crystals. We probe here how the crystal packing alters microsecond dynamics, using solid-state NMR measurements and multi-microsecond MD simulations of different crystal forms of ubiquitin. Near-Rotary-resonance Relaxation Dispersion (NERRD) experiments probe angular motion of the backbone on a microsecond time scale, while Bloch-McConnell Relaxation Dispersion data report on fluctuations of the local electronic environment. Combining these experimental data with MD simulations, we show that the packing of the protein can significantly alter the thermodynamics and kinetics of local conformational exchange. Moreover, we provide additional evidence for small-amplitude reorientational motion of protein molecules in the crystal lattice with a ∼3-5° amplitude on a tens-of-microseconds time scale in one of the crystals, but not in others. We find evidence that overall motion may be coupled to local dynamics, resulting in an extensive dynamic network involving both intra- and intermolecular motional modes. Our study highlights the importance of considering the packing when analyzing dynamics of crystalline proteins, and will be important for the emerging field of X-ray diffraction based dynamics studies.