|PROSITE documentation PDOC51120|
The low-density lipoprotein receptor (LDLR) regulates cholesterol homeostasis in mammalian cells. LDLR binds cholesterol-carrying LDL, associates with clathrin-coated pits, and is internalized into acidic endosomes where it separates from its ligand. The ligand is degraded in lysosomes, while the receptor returns to the cell surface . The LDLR has several domains. The ligand-binding domain contains seven LDL receptor class A repeats (see <PDOC00929>), each with three disulfide bonds and a coordinated Ca2+ ion. The second conserved region contains two EGF repeats (see <PDOC00913>), followed by six YWTD or LDL receptor class B repeats and another EGF repeat . This conserved region is critical for ligand release and recycling of the receptor .
The structure of the six YWTD repeats of LDL receptor have been solved (see <PDB:1IJQ>) . The six YWTD repeats together fold into a six-bladed β-propeller. Each blade of the propeller consists of four antiparallel β-strands; the innermost strand of each blade is labeled 1 and the outermost strand, 4. The sequence repeats are offset with respect to the blades of the propeller, such that any given 40-residue YWTD repeat spans strands 2-4 of one propeller blade and strand 1 of the subsequent blade. This offset ensures circularization of the propeller because the last strand of the final sequence repeat acts as an innermost strand 1 of the blade that harbors strands 2-4 from the first sequence repeat.
Some proteins known to contain LDL receptor class B repeats:
The profile we developed covers the whole LDL receptor class B repeat.Last update:
May 2005 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Brown M.S. Goldstein J.L.|
|Title||A receptor-mediated pathway for cholesterol homeostasis.|
|Title||An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components.|
|Source||J. Mol. Biol. 283:837-862(1998).|
|3||Authors||Davis C.G. Goldstein J.L. Sudhof T.C. Anderson R.G. Russell D.W. Brown M.S.|
|Title||Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region.|
|4||Authors||Jeon H. Meng W. Takagi J. Eck M.J. Springer T.A. Blacklow S.C.|
|Title||Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair.|
|Source||Nat. Struct. Biol. 8:499-504(2001).|