An atomistic characterisation of high-density lipoprotein subpopulation models and the conserved 'LN' region of ApoA-I

This study reveals that previously characterised ellipsoidal HDL3a and HDL2a models revert to a more spherical geometry in an atomistic representation due to the enhanced conformational flexibility afforded to the apoA-I protein secondary structure, allowing for enhanced surface lipid packing and lower overall surface hydrophobicity. Indeed, the proportional surface hydrophobicity and apoA-I exposure reduced with increasing HDL size, consistent with previous characterisations. Furthermore, solvent exposure of the 'LN' region of apoA-I was exclusively limited to the smallest HDL3c model within the timescale of the simulations, and typically corresponded with a distinct loss in secondary structure across the 'LN' region to form part of a significant contiguous hydrophobic patch on the HDL surface. Taken together, these findings provide preliminary evidence for a subpopulation-specific interaction between HDL3c particles and circulating hydrophobic species such as Aβ via the exposed 'LN' region of apoA-I.PMID:38555508 | DOI:10.1016/j.bpj.2024.03.039

Source: Biophysical Journal - March 31, 2024 Category: Physics Authors: Chris J Malajczuk Ricardo L Mancera Source Type: research