YWTD repeat

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,^[1] preproepidermal growth factor, and nidogen (entactin).^[2]

LDL receptor repeat class B
Identifiers
Symbol	Ldl_recept_b
Pfam	PF00058
InterPro	IPR000033
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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.^[3] 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.^[4] This conserved region is critical for ligand release and recycling of the receptor.^[5]

References

1. Russell DW, Schneider WJ, Yamamoto T, Brown MS, Goldstein JL, Davis CG, Casey ML (1984). "The human LDL receptor: a cysteine-rich protein with multiple Alu sequences in its mRNA". Cell. 39 (1): 27–38. doi:10.1016/0092-8674(84)90188-0. PMID 6091915.
2. Eck MJ, Springer TA, Blacklow SC, Takagi J, Jeon H, Meng W (2001). "Implications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair". Nat. Struct. Biol. 8 (6): 499–504. doi:10.1038/88556. PMID 11373616.
3. Brown MS, Goldstein JL (1986). "A receptor-mediated pathway for cholesterol homeostasis". Science. 232 (4746): 34–47. doi:10.1126/science.3513311. PMID 3513311.
4. Springer TA (1998). "An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components". J. Mol. Biol. 283 (4): 837–862. doi:10.1006/jmbi.1998.2115. PMID 9790844.
5. Russell DW, Brown MS, Goldstein JL, Davis CG, Sudhof TC, Anderson RG (1987). "Acid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region". Nature. 326 (6115): 760–765. doi:10.1038/326760a0. PMID 3494949.

This article incorporates text from the public domain Pfam and InterPro: IPR000033