{PDOC51120}
{PS51120; LDLRB}
{BEGIN}
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* LDL-receptor class B (LDLRB) repeat profile *
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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
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  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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: May 2005 / First entry.

[ 1] Brown M.S., Goldstein J.L.
     "A receptor-mediated pathway for cholesterol homeostasis."
     Science 232:34-47(1986).
     PubMed=3513311
[ 2] Springer T.A.
     "An extracellular beta-propeller module predicted in lipoprotein and
     scavenger receptors, tyrosine kinases, epidermal growth factor
     precursor, and extracellular matrix components."
     J. Mol. Biol. 283:837-862(1998).
     PubMed=9790844
[ 3] Davis C.G., Goldstein J.L., Sudhof T.C., Anderson R.G., Russell D.W.,
     Brown M.S.
     "Acid-dependent ligand dissociation and recycling of LDL receptor
     mediated by growth factor homology region."
     Nature 326:760-765(1987).
     PubMed=3494949; DOI=10.1038/326760a0
[ 4] Jeon H., Meng W., Takagi J., Eck M.J., Springer T.A., Blacklow S.C.
     "Implications for familial hypercholesterolemia from the structure of
     the LDL receptor YWTD-EGF domain pair."
     Nat. Struct. Biol. 8:499-504(2001).
     PubMed=11373616; DOI=10.1038/88556

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