M. Roos, M. Hofmann, S. Link,
M. Ott, J. Balbach, E. Rössler, K. Saalwächter, A. Krushelnitsky.
The ‘‘long tail’’ of the protein tumbling correlation function:
observation by 1H NMR relaxometry in a wide frequency and concentration range.
J. Biomol. NMR 63, 403-415 (2015).
Inter-protein interactions in solution affect the
auto-correlation function of Brownian tumbling not only in
terms of a simple increase of the correlation time, they also
lead to the appearance of a weak slow component (‘‘long
tail’’) of the correlation function due to a slowly changing
local anisotropy of the microenvironment. The conventional
protocol of correlation time estimation from the
relaxation rate ratio R1/R2 assumes a single-component
tumbling correlation function, and thus can provide
incorrect results as soon as the ‘‘long tail’’ is of relevance.
This effect, however, has been underestimated in many
instances. In this work we present a detailed systematic
study of the tumbling correlation function of two proteins,
lysozyme and bovine serum albumin, at different concentrations
and temperatures using proton field-cycling relaxometry
combined with R1ρ and R2 measurements. Unlike
high-field NMR relaxation methods, these techniques
enable a detailed study of dynamics on a time scale longer
than the normal protein tumbling correlation time and,
thus, a reliable estimate of the parameters of the ‘‘long
tail’’. In this work we analyze the concentration dependence
of the intensity and correlation time of the slow
component and perform simulations of high-field
15N NMR relaxation data demonstrating the importance of
taking the ‘‘long tail’’ in the analysis into account.