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. 2000 Sep;79(3):1679–1685. doi: 10.1016/S0006-3495(00)76417-4

Molecular belt models for the apolipoprotein A-I Paris and Milano mutations.

A E Klon 1, M K Jones 1, J P Segrest 1, S C Harvey 1
PMCID: PMC1301059  PMID: 10969027

Abstract

Models for the binding of the 200-residue carboxy-terminal domain of two mutants of apolipoprotein A-I (apo A-I), apo A-I(R173C)(Milano) and apo A-I(R151C)(Paris), to lipid in discoidal high-density lipoprotein (HDL) particles are presented. In both models, two monomers of the mutant apo A-I molecule bind to lipid in an antiparallel manner, with the long axes of their helical repeats running perpendicular to the normal of the lipid bilayer to form a single disulfide-linked homodimer. The overall structures of the models of these two mutants are very similar, differing only in helix-helix registration. Thus these models are consistent with experimental observations that reconstituted HDL particles containing apo A-I(Milano) and apo A-I(Paris) are very similar in diameter to reconstituted HDL particles containing wild-type apo A-I, and they support the belief that apo A-I binds to lipid in discoidal HDL particles via the belt conformation.

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Selected References

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