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PDBsum entry 1ndx
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Structural protein
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PDB id
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1ndx
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DOI no:
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J Mol Biol
283:837-862
(1998)
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PubMed id:
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An extracellular beta-propeller module predicted in lipoprotein and scavenger receptors, tyrosine kinases, epidermal growth factor precursor, and extracellular matrix components.
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T.A.Springer.
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ABSTRACT
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An abundant, widely dispersed, extracellular sequence repeat that contains a
consensus YWTD motif is shown here to occur in groups of six contiguous repeats.
Thirteen lines of evidence, including experimental and computational data,
predict with p<3x10(-9) that the repeats do not form tandem domains, but
rather each group of six repeats folds into a compact beta-propeller structure.
The six beta-sheets are arranged about a 6-fold pseudosymmetry axis, and each
repeat contributes loops to the faces surrounding the pseudosymmetry axis. Seven
different endocytic receptors that contain from one to eight YWTD beta-propeller
domains act as lipoprotein, vitellogenin, and scavenger receptors. In the low
density lipoprotein receptor (LDLR), the many mutations in familial
hypercholesterolaemia that map to the YWTD domain can now be interpreted. In the
extracellular matrix component nidogen, the YWTD domain functions to bind
laminin. Three YWTD domains and interspersed fibronectin type III (FN3) domains
constitute almost the entire extracellular domain of the sevenless and c-ros
receptor tyrosine kinases. YWTD domains often are bounded by epidermal growth
factor (EGF) modules, including in the EGF precursor itself. YWTD
beta-propellers have a circular folding pattern that brings neighboring modules
into close proximity, and may have important consequences for the architecture
of multi-domain proteins.
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Selected figure(s)
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Figure 4.
Figure 4. Topology and ribbon diagrams of the six-bladed
β-propeller domain predicted for the YWTD domain of nidogen. A,
Topology diagram, with each β-sheet given a different color.
Sequence repeats are separated by vertical broken lines. Note
the offset between sequence repeats and β-sheets. Each sheet is
termed a W, with each β-strand representing one leg of the W.
β-Strands are represented by arrows. The disulfide bonds in
nidogen between strands 2 and 3 of W4 and between the 1-2 loop
of W1 and the C-terminal segment in W6 are shown as gold lines.
B, Stereo view ribbon representation, with each β-sheet or
blade of the nidogen β-propeller model given the same color
code as in A. The 4-1 loops that connect each sheet are grey.
The view is up the 6-fold pseudosymmetry axis, with the
“bottom” of the propeller containing the strand 1 to 2
loops, the strand 3 to 4 loops, and the N and C termini of the
propeller domain in the foreground. C, Side view, with the 1-2,
3-4, and N and C termini upward. The side-chain bonds for the
cysteine residues in the two disulfide bonds of the nidogen
β-propeller domain are shown in gold. The β-strands shown as
ribbons are as defined by DSSP [Kabsch and Sander 1983] from the
nido model (see Figure 7 and Table 6). Prepared with MOLMOL
[Koradi et al 1996].
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Figure 6.
Figure 6. Threading scores for YWTD domains. A and B,
Average Z-scores for 89 YWTD domains related to LDLR (A) and 18
YWTD domains from sevenless and c-ros (B). Z-scores for each
structure were averaged for the 89 or 18 sequences using a
program written by Kemin Tan, and plotted with the histogram
tool of Microsoft Excel. The arrows mark 1gotB1. C, The
distribution of Z-scores for all 107 YWTD domain sequences for
the second highest hit, 2aaiB0, ricin β-trefoil domain; and the
top hit, 1gotB1, G protein β-propeller domain.
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The above figures are
reprinted
by permission from Elsevier:
J Mol Biol
(1998,
283,
837-862)
copyright 1998.
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Figures were
selected
by an automated process.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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The structure of MESD45-184 brings light into the mechanism of LDLR family folding.
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Structure,
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PDB codes:
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PDB codes:
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PDB code:
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M.Mekuchi,
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PDB code:
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N.Beglova,
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The LDL receptor: how acid pulls the trigger.
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Trends Biochem Sci,
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Association between bone mineral density and LDL receptor-related protein 5 gene polymorphisms in young Korean men.
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Cooperation between fixed and low pH-inducible interfaces controls lipoprotein release by the LDL receptor.
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Mol Cell,
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PDB code:
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R.A.Debose-Boyd
(2004).
Knowing when to let go: endosomal release of LDL from the LDL-Receptor.
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Mol Cell,
16,
160-162.
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D.M.Kamikura,
and
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Lipoprotein receptors and a disabled family cytoplasmic adaptor protein regulate EGL-17/FGF export in C. elegans.
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Genes Dev,
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Curr Opin Struct Biol,
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Coaxing the LDL receptor family into the fold.
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Cell,
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J.Takagi,
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J.H.Wang,
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Complex between nidogen and laminin fragments reveals a paradigmatic beta-propeller interface.
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Nature,
424,
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PDB code:
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D.D.Chang,
B.Q.Hoang,
J.Liu,
and
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(2002).
Molecular basis for interaction between Icap1 alpha PTB domain and beta 1 integrin.
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J Biol Chem,
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PDB code:
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H.Jing,
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Structure,
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PDB code:
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J.Herz,
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Gene structure and functional analysis of the mouse nidogen-2 gene: nidogen-2 is not essential for basement membrane formation in mice.
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Structure,
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Novel sequences propel familiar folds.
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Structure,
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Solution structure of the sixth LDL-A module of the LDL receptor.
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Biochemistry,
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PDB code:
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C.L.North,
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Evidence that familial hypercholesterolemia mutations of the LDL receptor cause limited local misfolding in an LDL-A module pair.
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Biochemistry,
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K.Dolmer,
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NMR solution structure of complement-like repeat CR3 from the low density lipoprotein receptor-related protein. Evidence for specific binding to the receptor binding domain of human alpha(2)-macroglobulin.
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J Biol Chem,
275,
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PDB code:
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O.M.Andersen,
P.A.Christensen,
L.L.Christensen,
C.Jacobsen,
S.K.Moestrup,
M.Etzerodt,
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(2000).
Specific binding of alpha-macroglobulin to complement-type repeat CR4 of the low-density lipoprotein receptor-related protein.
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Biochemistry,
39,
10627-10633.
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S.H.Kang,
and
J.M.Kramer
(2000).
Nidogen is nonessential and not required for normal type IV collagen localization in Caenorhabditis elegans.
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Mol Biol Cell,
11,
3911-3923.
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T.Kirchhausen
(2000).
Clathrin.
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Annu Rev Biochem,
69,
699-727.
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Y.Av-Gay,
and
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(2000).
The eukaryotic-like Ser/Thr protein kinases of Mycobacterium tuberculosis.
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Trends Microbiol,
8,
238-244.
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B.Grant,
and
D.Hirsh
(1999).
Receptor-mediated endocytosis in the Caenorhabditis elegans oocyte.
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Mol Biol Cell,
10,
4311-4326.
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C.Abergel,
E.Bouveret,
J.M.Claverie,
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A.Rigal,
C.Lazdunski,
and
H.Bénédetti
(1999).
Structure of the Escherichia coli TolB protein determined by MAD methods at 1.95 A resolution.
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| |
Structure,
7,
1291-1300.
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PDB code:
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V.Fülöp,
and
D.T.Jones
(1999).
Beta propellers: structural rigidity and functional diversity.
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Curr Opin Struct Biol,
9,
715-721.
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}
}
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