Assembly of lipids and proteins into lipoprotein particles.
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 micros 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.
Shih
Amy Y
AY
Center for Biophysics and Computational Biology, Beckman Institute for Advance Science and Technology, Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
Arkhipov
Anton
A
Freddolino
Lydia
L
Sligar
Stephen G
SG
Schulten
Klaus
K
D003198:Computer Simulation; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008074:Lipoproteins / Q000737:chemistry*; D008958:Models, Molecular; D053758:Nanoparticles / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D053838:Scattering, Small Angle; D012997:Solvents; D014961:X-Ray Diffraction
D008055:Lipids; D008074:Lipoproteins; D011506:Proteins; D012997:Solvents