Human LDLR PE-conjugated Antibody

The Low Density Lipoprotein Receptor (LDL R) is the founding member of the LDL R family of scavenger receptors (1, 2). This family contains transmembrane molecules that are characterized by the presence of EGF repeats, complement-like repeats, and YWTD motifs that form beta-propellers. Although members of the family were originally thought to be endocytic receptors, it is now clear that some members interact with adjacent cell-surface molecules, expanding their range of activities (2). Human LDL R is synthesized as an 860 amino acid (aa) precursor that contains a 21 aa signal sequence, a 767 aa extracellular region, a 22 aa transmembrane segment and a 50 aa cytoplasmic tail (3). The extracellular region is complex. It consists of seven N-terminal complement-like cysteine-rich repeats that bind ligand. Cysteine residues in this region participate in intrachain disulfide bonds. This region is followed by three EGF-like repeats with a beta-propeller YWTD containing motif. The EGF-like repeats are responsible for ligand bonding and dissociation. Finally, there is a 50 aa membrane proximal Ser/Thr-rich region that serves as a carbohydrate attachment point (1, 3, 4). There is extensive O-linked and modest N-linked glycosylation. Thus the receptor’s predicted molecular weight of 93 kDa is increased to a native molecular weight of 120-160 kDa (3, 4). Within the 50 aa cytoplasmic tail, there is an NPXY motif that links the receptor to clathrin pits (1). The extracellular region of human LDL R is 51% aa identical to the extracellular region of human VLDL R, and 79% aa identical to the extracellular region of mouse LDL R. LDL R is constitutively expressed and binds ApoB of LDL and ApoE of VLDL (5). It is responsible for clearing 70% of plasma LDL in liver (5). Mutations in the LDL R gene cause the autosomal dominant disorder, familial hypercholesterolemia (6).