Current concepts on the formation of discoidal apolipoprotein A-I lipid bound complexes: From picket fences to a double-belt model via inter-ring rotation of apolipoprotein A-I monomers

Research output: Chapter in Book/Report/Conference proceedingChapter

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. Additional recent research has indicated that there is a possibility of inter-ring rotation between the two monomers about the lipid unilamellar bilayer core. For instance, from well-known mutations, 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. Current research shows that from a computational perspective, the independent inter-ring rotation of the two alpha-helical monomers about the lipid unilamellar bilayer core is feasible. And, such simulations support the existing double-belt model. Other long time scale dynamics simulations are very revealing of the discoidal behavior having preferred out-of-plane shapes akin to a saddle-point. However, despite all of the indicated deformations, the rotation of the two protein monomers is able to occur with biasing. It was determined that a cysteine mutant at Glu107 as a possible target for future mutational studies. Several other biophysical studies are discussed in light of these recent findings to bring a greater understanding to ApoA-I dynamic motion and registration shifts. Since HDL remodeling is necessary for cholesterol transport, our model for remodeling through dynamics has substantial biomedical implications.

Original languageEnglish (US)
Title of host publicationApolipoproteins
Subtitle of host publicationRegulatory Functions, Health Effects and Role in Disease
PublisherNova Science Publishers, Inc.
Pages35-55
Number of pages21
ISBN (Print)9781622574841
StatePublished - Oct 1 2012

Keywords

  • Apolipoprotein A-I
  • Discoidal high density lipoprotein
  • Double belt model
  • HDL
  • Milano mutant
  • Paris mutant
  • Simulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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