Abstract
The double belt model for lipid-bound discoidal apolipoprotein A-I consists of two alpha-helical monomers bound about an unilamellar bilayer of lipids. Previous work, based on salt bridge calculations, has demonstrated that the L5/5 registration, Milano mutant, and Paris mutant are preferred conformations for apolipoprotein A-I. The salt bridge scoring indicated better energetic scoring in these alignments. The Paris (R151C) and Milano (R173C) mutants indicate a mode of change must be available. To find proper registration, one proposed change is a 'rotationally' independent circular motion of the two protein monomers about the lipid unilamellar bilayer core. Here, we present computational data for independent inter-ring rotation of the two alpha-helical monomers about the lipid unilamellar bilayer core. The simulations presented here support the existing double-belt model. We find the rotation of the two protein monomers is able to occur with biasing. We determine that a cysteine mutant at Glu107 as a possible target for future mutational studies. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling through dynamics has substantial biomedical implications.
Original language | English (US) |
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Pages (from-to) | 1006-1014 |
Number of pages | 9 |
Journal | Journal of Molecular Graphics and Modelling |
Volume | 29 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2011 |
Keywords
- Apolipoprotein A-I
- Discoidal high density lipoprotein
- Double belt model
- HDL
- Milano mutant
- Paris mutant
- Simulation
ASJC Scopus subject areas
- Spectroscopy
- Physical and Theoretical Chemistry
- Computer Graphics and Computer-Aided Design
- Materials Chemistry