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PDBsum entry 1d2l
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Signaling protein
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PDB id
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1d2l
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Contents |
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* Residue conservation analysis
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References listed in PDB file
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Key reference
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Title
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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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Authors
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K.Dolmer,
W.Huang,
P.G.Gettins.
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Ref.
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J Biol Chem, 2000,
275,
3264-3269.
[DOI no: ]
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PubMed id
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Abstract
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We have used NMR methods to determine the structure of the calcium complex of
complement-like repeat 3 (CR3) from the low density lipoprotein receptor-related
protein (LRP) and to examine its specific interaction with the receptor binding
domain of human alpha(2)-macroglobulin. CR3 is one of eight related repeats that
constitute a major ligand binding region of LRP. The structure is very similar
in overall fold to homologous complement-like repeat CR8 from LRP and
complement-like repeats LB1, LB2, and LB5 from the low density lipoprotein
receptor and contains a short two-strand antiparallel beta-sheet, a one turn
alpha-helix, and a high affinity calcium site with coordination from four
carboxyls and two backbone carbonyls. The surface electrostatics and topography
are, however, quite distinct from each of these other repeats. Two-dimensional
(1)H,(15)N-heteronuclear single quantum coherence spectra provide evidence for a
specific, though relatively weak (K(d) approximately 140 microM), interaction
between CR3 and human alpha2-macroglobulin receptor binding domain that involves
a contiguous patch of surface residues in the central region of CR3. This
specific interaction is consistent with a mode of LRP binding to ligands that
uses contributions from more than one domain to generate a wide array of
different binding sites, each with overall high affinity.
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Figure 1.
Fig. 1. Primary structures of complement-like repeats
from cluster II of human LRP. Residues Gln 833 (residue 5 of
CR3) to Asp1163 of LRP are aligned based on the positions of the
conserved six cysteines present in each complement-like repeat
of this cluster. The numbering is for the CR3 construct used in
the present study, which also contains the residues GSPP prior
to the sequence in the figure; with GS (residues 1 and 2)
arising as a result of the glutathione S-transferase fusion
protein cleavage site and not being present in LRP. Residues
that are shaded are those that have been shown to coordinate the
calcium in LB5 from LDLR (23) and in CR3 and CR8 from LRP. These
are entirely conserved within this cluster, with the exception
of CR10, which has K in place of W at position 23.
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Figure 2.
Fig. 2. NMR structures of CR3. Left side, stereo view of
20 best structures of CR3. Right side, ribbon representation of
CR3 showing proposed location of the calcium binding site (green
sphere).
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2000,
275,
3264-3269)
copyright 2000.
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