VLDL Receptor - Protein Structure

Protein Structure

VLDLR is a member of the low-density-lipoprotein (LDL) receptor family, which is entirely composed of type I transmembrane lipoprotein receptors.

All members of this family share five highly conserved structural domains: an extracellular N-terminal ligand-binding domain with cysteine-rich repeats (also called ligand-binding repeats), an epidermal growth factor (EGF), an O-linked glycosylation sugar domain, a single transmembrane sequence, and a cytoplasmic domain which contains an NPxY sequence. The NPxY motif functions in signal transduction and the targeting of receptors to coated pits and consists of the sequence Asparagine-Proline-X-Tyrosine, where X can be any amino acid. Mimicking this general structure, VLDLR has eight, 40 amino acid long cysteine-rich repeats in its extracellular N-terminal ligand-binding domain. This is the main difference from the main member of the LDL receptor family, LDLR, which has only seven cysteine-rich repeats which are also 40 amino acids long. Each of these cysteine-rich repeats, in both VLDLR and LDLR, has three disulfide bonds and a coordinated Ca2+ ion. The N-terminus also consists of a glycine residue followed by 27 hydrophobic residues that constitute the signal peptide. Following this region is an EGF repeat, a β-propeller segment that plays a role in the pH-dependent dissociation of the ligand-receptor complex, and two more EGF repeats. The VLDLR O-linked glycosylation domain, next in the sequence, has many threonine and serine residues and totals 46 amino acids. The transmembrane domain, which functions in anchoring the receptors to the membrane, is 22 amino acids long. Final in the sequence is the 54 amino acid cytoplasmic domain, which contains the NPxY motif.