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PDBsum entry 2jd4
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Metal binding protein
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PDB id
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2jd4
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References listed in PDB file
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Key reference
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Title
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Crystal structure and cell surface anchorage sites of laminin alpha1lg4-5.
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Authors
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D.Harrison,
S.A.Hussain,
A.C.Combs,
J.M.Ervasti,
P.D.Yurchenco,
E.Hohenester.
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Ref.
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J Biol Chem, 2007,
282,
11573-11581.
[DOI no: ]
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PubMed id
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Note: In the PDB file this reference is
annotated as "TO BE PUBLISHED". The citation details given above have
been manually determined.
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Abstract
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The laminin G-like (LG) domains of laminin-111, a glycoprotein widely expressed
during embryogenesis, provide cell anchoring and receptor binding sites that are
involved in basement membrane assembly and cell signaling. We now report the
crystal structure of the laminin alpha1LG4-5 domains and provide a mutational
analysis of heparin, alpha-dystroglycan, and galactosylsulfatide binding. The
two domains of alpha1LG4-5 are arranged in a V-shaped fashion similar to that
observed with laminin alpha2 LG4-5 but with a substantially different
interdomain angle. Recombinant alpha1LG4-5 binding to heparin,
alpha-dystroglycan, and sulfatides was dependent upon both shared and unique
contributions from basic residues distributed in several clusters on the surface
of LG4. For heparin, the greatest contribution was detected from two clusters,
2719RKR and 2791KRK. Binding to alpha-dystroglycan was particularly dependent on
basic residues within 2719RKR, 2831RAR, and 2858KDR. Binding to
galactosylsulfatide was most affected by mutations in 2831RAR and 2766KGRTK but
not in 2719RKR. The combined analysis of structure and activities reveal
differences in LG domain interactions that should enable dissection of
biological roles of different laminin ligands.
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Figure 1.
FIGURE 1. Structure of laminin  1LG4-5. A,
superposition of the two 1LG4-5 molecules in the
asymmetric unit. Molecules A (mol A; light brown) and B (mol B;
blue) were superimposed on their LG4 domains. The position of
Tyr^2871 (see"Results") is indicated. B, schematic diagram of
molecule B (cyan, LG4; green, LG5). The N and C termini are
labeled. Disulfide bonds are shown as yellow ball-and-stick
models. Metal ions are shown as purple spheres. The positions of
Asn^2714 and Asn^2811 (N-linked glycosylation sites) and
Cys^3014 (unpaired cysteine) are indicated. The third
glycosylation site at Asn^2900 is located at the back of LG5.
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Figure 2.
FIGURE 2. Comparison of 1LG4-5 and 2LG4-5.
A, sequence alignment of 1LG4-5 and 2LG4-5.
Identical residues are shaded yellow, cysteines are shaded
black, and metal ion ligands are shaded purple. The sequence
numbering and  -strands of mouse 1LG4-5
are indicated above the alignment, and the sequence numbering of
mouse 2LG4-5 is indicated
below the alignment. Residues implicated in receptor binding to
1LG4-5 (this work) and
2LG4-5 (13) are
indicated in red. B, superposition of 1LG4 (this work) and
2LG4 (8). A total of
148 C atoms were superimposed
with a root mean square deviation of 0.91 Å. C,
superposition of 1LG5 (this work) and
2LG5 (8). A total of
153 C atoms were superimposed
with a root mean square deviation of 0.59 Å.
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The above figures are
reprinted
by permission from the ASBMB:
J Biol Chem
(2007,
282,
11573-11581)
copyright 2007.
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Secondary reference #1
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Title
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Structure of the c-Terminal laminin g-Like domain pair of the laminin alpha2 chain harbouring binding sites for alpha-Dystroglycan and heparin.
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Authors
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D.Tisi,
J.F.Talts,
R.Timpl,
E.Hohenester.
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Ref.
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EMBO J, 2000,
19,
1432-1440.
[DOI no: ]
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PubMed id
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Figure 2.
Figure 2 (A) The LG4–LG5 interface. The colour scheme is the
same as in Figure 1. Residues involved in inter-domain contacts
are shown as ball-and-stick models and are labelled. The most
prominent contact is centred on Phe2931 (see the text). (B)
Interactions between the N-terminal segment (in brown) and LG5
(in green). Dashed lines indicate hydrogen bonds. The electron
density shown is a simulated annealing 2F[obs] - F[calc] omit
map at 2.0 Å resolution (1.5  contouring),
in which the N-terminal segment and Cys3017 in LG5 were excluded
from the phasing model.
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Figure 4.
Figure 4 Calcium-binding sites in  2LG4–5.
(A) Calcium 1 in LG4. The calcium ligands are shown as
ball-and-stick models and are labelled. Calcium–ligand bonds
are shown as black sticks. A metal-bound water molecule is shown
in yellow. (B) Calcium 2 in LG5. The calcium coordination is
similar to calcium 1, but Asp2861 from a packing-related
molecule in the crystal (in yellow) occupies the fifth
coordination site (see the text).
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The above figures are
reproduced from the cited reference
which is an Open Access publication published by Macmillan Publishers Ltd
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Secondary reference #2
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Title
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Laminin functions in tissue morphogenesis.
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Authors
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J.H.Miner,
P.D.Yurchenco.
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Ref.
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Annu Rev Cell Dev Biol, 2004,
20,
255-284.
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PubMed id
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