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PDBsum entry 3k66
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Cell adhesion
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PDB id
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3k66
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References listed in PDB file
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Key reference
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Title
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Structural characterization of the e2 domain of apl-1, A caenorhabditis elegans homolog of human amyloid precursor protein, And its heparin binding site.
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Authors
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J.T.Hoopes,
X.Liu,
X.Xu,
B.Demeler,
E.Folta-Stogniew,
C.Li,
Y.Ha.
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Ref.
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J Biol Chem, 2010,
285,
2165-2173.
[DOI no: ]
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PubMed id
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Abstract
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The amyloid beta-peptide deposit found in the brain tissue of patients with
Alzheimer disease is derived from a large heparin-binding protein precursor APP.
The biological function of APP and its homologs is not precisely known. Here we
report the x-ray structure of the E2 domain of APL-1, an APP homolog in
Caenorhabditis elegans, and compare it to the human APP structure. We also
describe the structure of APL-1 E2 in complex with sucrose octasulfate, a highly
negatively charged disaccharide, which reveals an unexpected binding pocket
between the two halves of E2. Based on the crystal structure, we are able to
map, using site-directed mutagenesis, a surface groove on E2 to which heparin
may bind. Our biochemical data also indicate that the affinity of E2 for heparin
is influenced by pH: at pH 5, the binding appears to be much stronger than that
at neutral pH. This property is likely caused by histidine residues in the
vicinity of the mapped heparin binding site and could be important for the
proposed adhesive function of APL-1.
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Figure 2.
Structural comparison between APL-1 and APP. A, superposition
of APP E2 (red: PDB entry 1rw6) onto the N-terminal subdomain of
APL-1 E2 (black). The Cα traces are shown in stereo pairs. B,
superposition of APP E2 (red: x-ray structure PDB entry 1rw6;
green: NMR structure PDB entry 1tkn) onto the C-terminal
subdomain of APL-1 E2 (black). These images were generated by
Molscript (37).
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Figure 5.
SOS was bound between the two halves of E2. A, binding site
was near the middle of the molecule. B, detailed view of the
sulfated glucose moiety of SOS, and its interactions with the
protein. The six carbon atoms (C1–C6) of the glucose ring are
labeled. The dotted lines represent hydrogen bonds. The side
chain of Lys-372 is not visible in the electron density map, but
its position on αD is indicated.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2010,
285,
2165-2173)
copyright 2010.
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Secondary reference #1
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Title
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The X-Ray structure of an antiparallel dimer of the human amyloid precursor protein e2 domain.
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Authors
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Y.Wang,
Y.Ha.
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Ref.
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Mol Cell, 2004,
15,
343-353.
[DOI no: ]
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PubMed id
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Figure 1.
Figure 1. Domain Structure of Human APP Isoform-751
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Figure 6.
Figure 6. Models of Membrane-Bound APP
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The above figures are
reproduced from the cited reference
with permission from Cell Press
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