Assembly of Lipids and Proteins into Lipoprotein Particles
mediaposted on 27.09.2007 by Amy Y. Shih, Anton Arkhipov, Peter L. Freddolino, Stephen G. Sligar, Klaus Schulten
Media is any form of research output that is recorded and played. This is most commonly video, but can be audio or 3D representations.
The self-assembly of reconstituted discoidal high-density lipoproteins, known as nanodiscs, was studied using coarse-grained molecular dynamics and small-angle X-ray scattering. In humans, high-density lipoprotein particles transport cholesterol in the blood and facilitate the removal of excess cholesterol from the body. Native high-density lipoprotein exhibits a wide variety of shapes and sizes, forming lipid-free/poor, nascent discoidal, and mature spherical particles. Little is known about how these lipoprotein particles assemble and transform from one state to another. Multiple 10 μs coarse-grained simulations reveal the assembly of discoidal high-density lipoprotein particles from disordered protein−lipid complexes. Small-angle X-ray scattering patterns were calculated from the final assembled structures and compared with experimental measurements carried out for this study to verify the accuracy of the coarse-grained simulations. Results show that hydrophobic interactions assemble, within several microseconds, the amphipathic helical proteins and lipids into roughly discoidal particles, while the proteins assume a final approximate double-belt configuration on a slower time scale.