Apolipoprotein A-I assumes a "looped belt" conformation on reconstituted high density lipoprotein.

摘要: Apolipoprotein A-I (apoA-I) plays a central role in the reverse cholesterol transport pathway; however, structural basis for its antiatherogenic effects remains poorly understood. Here we employ EPR spectroscopy and fluorescence resonance energy transfer to elucidate conformation relative alignment of apoA-I monomers on discoidal (9.4 nm) reconstituted high density lipoprotein (rHDL). provided evidence an extended helical secondary structure. Position 139 since it was only residue examined display dynamic motional character consistent with flexible loop The spectra nitroxide probes at positions 133 146 exhibit spin coupling, indicating that these are proximal paired counterpart perimeter rHDL. studies employing engineered variants possessing single tryptophan (energy donor) and/or cysteine (whose thiol moiety covalently labeled extrinsic acceptor) molecules around rHDL align antiparallel conformation. Taken together observation positioned intervening sequence (134-145) do not this has led us propose "looped belt" model, wherein residues 133-146 comprise segment confers intrinsic ability adapt structure accommodate changing particle lipid content. Specifically, looped belt exception amino acids 134-145, aligns helix 5-helix 5 registry, centered position 139.