Structure of a Complex Between the Pair of the LDL Receptor Ligand-Binding Modules 3-4 and the Receptor Associated Protein (RAP).
[AMRP_HUMAN] Note=In complex with the alpha-2-MR or gp330, it may have some role in the pathogenesis of membrane glomerular nephritis. [LDLR_HUMAN] Defects in LDLR are the cause of familial hypercholesterolemia (FH) [MIM:143890]; a common autosomal semi-dominant disease that affects about 1 in 500 individuals. The receptor defect impairs the catabolism of LDL, and the resultant elevation in plasma LDL-cholesterol promotes deposition of cholesterol in the skin (xanthelasma), tendons (xanthomas), and coronary arteries (atherosclerosis).                               [:]           
[AMRP_HUMAN] Interacts with LRP1/alpha-2-macroglobulin receptor and glycoprotein 330. [LDLR_HUMAN] Binds LDL, the major cholesterol-carrying lipoprotein of plasma, and transports it into cells by endocytosis. In order to be internalized, the receptor-ligand complexes must first cluster into clathrin-coated pits. In case of HIV-1 infection, functions as a receptor for extracellular Tat in neurons, mediating its internalization in uninfected cells.
Publication Abstract from PubMed
Proteins of the low-density lipoprotein receptor (LDLR) family are remarkable in their ability to bind an extremely diverse range of protein and lipoprotein ligands, yet the basis for ligand recognition is poorly understood. Here, we report the 1.26 A X-ray structure of a complex between a two-module region of the ligand binding domain of the LDLR and the third domain of RAP, an escort protein for LDLR family members. The RAP domain forms a three-helix bundle with two docking sites, one for each LDLR module. The mode of recognition at each site is virtually identical: three conserved, calcium-coordinating acidic residues from each LDLR module encircle a lysine side chain protruding from the second helix of RAP. This metal-dependent mode of electrostatic recognition, together with avidity effects resulting from the use of multiple sites, represents a general binding strategy likely to apply in the binding of other basic ligands to LDLR family proteins.
Structure of an LDLR-RAP complex reveals a general mode for ligand recognition by lipoprotein receptors.,Fisher C, Beglova N, Blacklow SC Mol Cell. 2006 Apr 21;22(2):277-83. PMID:16630895
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.