The low-density lipoprotein receptor: Ligands, debates and lore

Like pieces belonging to a large mosaic, the structures of low-density lipoprotein receptor (LDL-R) modules have been elucidated one by one in recent years. LDL-Rs localized on hepatocytes play an important role in removing cholesterol-transporting LDL particles from the plasma by receptor-mediated endocytosis. Key steps in this process involve the LDL-R binding LDL at neutral pH at the cell surface and, after internalization, releasing it again at acidic pH in the endosomes. How the modules of the LDL-R might interact within the intact receptor to carry out ligand binding and release has been revealed by the recent crystal structure of the extracellular domain of the LDL-R.