FEBS J. 2026 Feb 17. doi: 10.1111/febs.70451. Online ahead of print.
ABSTRACT
Cardiovascular disease is a major cause of human morbidity and mortality. Drug strategies for the prevention of the disease are largely centered on the interaction of low-density lipoprotein receptor (LDLR) with the apolipoprotein B-100 (apoB-100) protein on low-density lipoprotein (LDL). Recently, the structure of apoB-100 on LDL was determined in the absence and presence of LDLR, using cryo-electron microscopy. A remarkable structural feature of apoB-100 is the lack of any significant tertiary structure within the C-terminal two-thirds of the protein (>3000 residues). Instead, apoB-100 forms amphipathic helices and β-sheets on the phospholipid surface of LDL, which envelops its neutral lipid core. The apoB-100 ligand binding domain for LDLR includes multiple points on a circumferential β-belt and on the N terminus. In the course of this study, we also observed several instances of structural heterogeneity in apoB-100. The various conformations may allow apoB-100 to accommodate different size lipoprotein particles and to permit recognition by other apolipoproteins or receptors.
PMID:41700118 | DOI:10.1111/febs.70451