Practice question

Maintenance systemic cholesterol homeostasis depends precise receptor-mediated recognition apolipoproteins decorating lipoproteins. Low-density lipoprotein particles contain single copy apolipoprotein B-100 enormous 4536 amino acid amphipathic protein wrapping hydrophobic cholesteryl ester core exposing receptor binding domain rich basic arginine lysine around 3000-4000 position. LDL receptor extracellular region comprises seven cysteine-rich ligand-binding repeats LA1-LA7 each coordinating calcium via acidic residues Complementarity to basic ligand. Additional EGF precursor homology domain beta-propeller responsible acid-dependent ligand release endosome pH 5.5 conformational change. After synthesis ER folded with Rap chaperone processed Golgi receptors reside plasma membrane clustering coated pits via cytosolic FXNPXY interaction indirectly via ARH Dab2 adaptors linking AP2 mu2 beta2. Binding LDL neutral pH triggers rapid internalization minutes; LDL degraded lysosomes cholesterol esters hydrolyzed acid lipase releasing free cholesterol suppressing SREBP pathway HMG-CoA reductase. Transferrin receptor binds iron-laden transferrin distinct site handles iron not lipoproteins. LDL receptor does not function ubiquitin ligase or proteasome regulator. Specificity apoB-100 defines receptor linking endocytosis whole-body cholesterol balance physiology.