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Structures and Dynamics of Anionic Lipoprotein Nanodiscs
Published
Author(s)
D. Sweeney, Susan T. Krueger, Kakali Sen, John Hackett
Abstract
Nanolipoprotein particles known as nanodiscs (NDs) have emerged as versatile and powerful tools for the stabilization of mem-brane proteins permitting a plethora of structural and biophysical studies. Part of their allure is their flexibility to accommodate many types of lipids and precise control of the composition. However, little is known about how variations in lipid composition impact their structures and dynamics. Herein, we investigate how introduction of the anionic lipid POPG into POPC NDs impacts these features. Small-angle X-ray and neutron scattering (SAXS and SANS) of variable-composition NDs are complemented with molecular dynamics simulations to interrogate how increasing concentrations of POPG impacts ND shape, structure of the lipid core, as well as the dynamics of the popular membrane scaffold protein, MSP1D1(-). A convenient benefit of including POPG is that it eliminates D2O-induced aggregation observed in pure POPC NDs, permitting studies by SANS at multiple contrasts. SAXS and SANS data could be globally fit to a stacked elliptical cylinder model as well as an extension of the model that accounts for membrane curvature. Fitting to both models supports that introduction of POPG results in strongly elliptical nanodiscs, however MD simulations predict curvature of the membrane thereby supporting use of the latter model. Trends in the model-independent parameters suggest that increases in POPG reduce the conformational heterogeneity of the MSP1D1(-), which is agreement with MD simulations that show that the incorporation sufficient POPG results in disengagement of the N-terminal helix from the lipid core. These studies highlight novel structural changes in NDs in response to an anionic lipid and will inform the interpretation of future structural studies of membrane proteins embedded in NDs of mixed lipid composition.
Sweeney, D.
, Krueger, S.
, Sen, K.
and Hackett, J.
(2022),
Structures and Dynamics of Anionic Lipoprotein Nanodiscs, Journal of Physical Chemistry B
(Accessed October 13, 2024)