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PROSITE documentation PDOC51120 [for PROSITE entry PS51120]

LDL-receptor class B (LDLRB) repeat profile





Description

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 [1]. 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 [2]. This conserved region is critical for ligand release and recycling of the receptor [3].

The structure of the six YWTD repeats of LDL receptor have been solved (see <PDB:1IJQ>) [4]. 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:

  • Animal low-density lipoprotein receptor.
  • Mammalian pro-epidermal growth factor precursor (EGF).
  • Mammalian nidogen-2 precursor, a cell adhesion glycoprotein which is widely distributed in basement membranes.
  • Vertebrate sortilin-related receptor precursor.
  • Very low-density lipoprotein receptor precursor (VLDLR). It binds VLDL and transports it into cells by endocytosis.
  • Drosophila Yolkless protein. It is involved in uptake of vitellogenin by endocytosis.

The profile we developed covers the whole LDL receptor class B repeat.

Last update:

May 2005 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

LDLRB, PS51120; LDL-receptor class B (LDLRB) repeat profile  (MATRIX)


References

1AuthorsBrown M.S. Goldstein J.L.
TitleA receptor-mediated pathway for cholesterol homeostasis.
SourceScience 232:34-47(1986).
PubMed ID3513311

2AuthorsSpringer T.A.
TitleAn extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components.
SourceJ. Mol. Biol. 283:837-862(1998).
PubMed ID9790844

3AuthorsDavis C.G. Goldstein J.L. Sudhof T.C. Anderson R.G. Russell D.W. Brown M.S.
TitleAcid-dependent ligand dissociation and recycling of LDL receptor mediated by growth factor homology region.
SourceNature 326:760-765(1987).
PubMed ID3494949
DOI10.1038/326760a0

4AuthorsJeon H. Meng W. Takagi J. Eck M.J. Springer T.A. Blacklow S.C.
TitleImplications for familial hypercholesterolemia from the structure of the LDL receptor YWTD-EGF domain pair.
SourceNat. Struct. Biol. 8:499-504(2001).
PubMed ID11373616
DOI10.1038/88556



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