YWTD repeat
{{Pfam box
|Pfam=PF00058
|Name=LDL receptor repeat class B
|Symbol=Ldl_recept_b
|InterPro=IPR000033}}
YWTD repeats are four-stranded beta-propeller repeats found in low-density lipoprotein receptors (LDLR). The six YWTD repeats together fold into a six-bladed beta-propeller ({{InterPro|IPR011042}}). 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,{{cite journal |vauthors=Russell DW, Schneider WJ, Yamamoto T, Brown MS, Goldstein JL, Davis CG, Casey ML |title=The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA |journal=Cell |volume=39 |issue=1 |pages=27–38 |year=1984 |pmid=6091915 |doi=10.1016/0092-8674(84)90188-0}} preproepidermal growth factor, and nidogen (entactin).{{cite journal |vauthors=Eck MJ, Springer TA, Blacklow SC, Takagi J, Jeon H, Meng W |title=Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair |journal=Nat. Struct. Biol. |volume=8 |issue=6 |pages=499–504 |year=2001 |pmid=11373616 |doi=10.1038/88556}}
The 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.{{cite journal |vauthors=Brown MS, Goldstein JL |title=A receptor-mediated pathway for cholesterol homeostasis |journal=Science |volume=232 |issue=4746 |pages=34–47 |year=1986 |pmid=3513311 |doi=10.1126/science.3513311}} The LDLR has several domains. The ligand-binding domain contains seven LDL receptor class A repeats, each with three disulphide bonds and a coordinated Ca2+ ion. The second conserved region contains two EGF repeats, followed by six YWTD or LDL receptor class B repeats and another EGF repeat.{{cite journal|author=Springer TA |title=An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components |journal=J. Mol. Biol. |volume=283 |issue=4 |pages=837–862 |year=1998|pmid=9790844|doi=10.1006/jmbi.1998.2115}} This conserved region is critical for ligand release and recycling of the receptor.{{cite journal |vauthors=Russell DW, Brown MS, Goldstein JL, Davis CG, Sudhof TC, Anderson RG |title=Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region |journal=Nature |volume=326 |issue=6115 |pages=760–765 |year=1987 |pmid=3494949 |doi=10.1038/326760a0}}