InterPro : IPR000033

Name  LDLR class B repeat Short Name  LDLR_classB_rpt
Type  Repeat Description  The low-density lipoprotein receptor (LDLR) is the major cholesterol-carrying lipoprotein of plasma, acting to regulate cholesterol homeostasis in mammalian cells. The LDL receptor binds LDL and transports it into cells by acidic endocytosis. In order to be internalized, the receptor-ligand complex must first cluster into clathrin-coated pits. Once inside the cell, the LDLR separates from its ligand, which is degraded in the lysosomes, while the receptor returns to the cell surface []. The internal dissociation of the LDLR with its ligand is mediated by proton pumps within the walls of the endosome that lower the pH. The LDLR is a multi-domain protein, containing: The ligand-binding domain contains seven or eight 40-amino acid LDLR class A (cysteine-rich) repeats, each of which contains a coordinated calcium ion and six cysteine residues involved in disulphide bond formation []. Similar domains have been found in other extracellular and membrane proteins []. The second conserved region contains two EGF repeats, followed by six LDLR class B (YWTD) repeats, and another EGF repeat. The LDLR class B repeats each contain a conserved YWTD motif, and is predicted to form a beta-propeller structure []. This region is critical for ligand release and recycling of the receptor [].The third domain is rich in serine and threonine residues and contains clustered O-linked carbohydrate chains.The fourth domain is the hydrophobic transmembrane region.The fifth domain is the cytoplasmic tail that directs the receptor to clathrin-coated pits.LDLR is closely related in structure to several other receptors, including LRP1, LRP1b, megalin/LRP2, VLDL receptor, lipoprotein receptor, MEGF7/LRP4, and LRP8/apolipoprotein E receptor2); these proteins participate in a wide range of physiological processes, including the regulation of lipid metabolism, protection against atherosclerosis, neurodevelopment, and transport of nutrients and vitamins [].This entry represents the LDLR classB (YWTD) repeat, the structure of which has been solved []. The six YWTD repeats together fold into a six-bladed beta-propeller. Each blade of the propeller consists of four antiparallel beta-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 24 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 24 from the first sequence repeat. The repeat is found in a variety of proteins that include, vitellogenin receptor from Drosophila melanogaster, low-density lipoprotein (LDL) receptor [], preproepidermal growth factor, and nidogen (entactin).

Sequence Features

GO Displayer


InterPro protein domain ID --> Contigs



0 Child Features

0 Contains

3 Found In

Id Name Short Name Type
IPR011042 Six-bladed beta-propeller, TolB-like 6-blade_b-propeller_TolB-like Domain
IPR016317 Pro-epidermal growth factor Pro-epidermal_GF Family
IPR017049 Low density lipoprotein receptor-related protein, 5/6 Low_density_Lipo_rcpt-rel_p5/6 Family

0 Parent Features

7 Publications

First Author Title Year Journal Volume Pages
Yamamoto T The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA. 1984 Cell 39 27-38
Springer TA An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components. 1998 J Mol Biol 283 837-62
Daly NL Three-dimensional structure of a cysteine-rich repeat from the low-density lipoprotein receptor. 1995 Proc Natl Acad Sci U S A 92 6334-8
Brown MS A receptor-mediated pathway for cholesterol homeostasis. 1986 Science 232 34-47
Davis CG Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region. 1987 Nature 326 760-5
Jeon H Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair. 2001 Nat Struct Biol 8 499-504
May P The LDL receptor-related protein (LRP) family: an old family of proteins with new physiological functions. 2007 Ann Med 39 219-28

To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)