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PDBsum entry 1pz8
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Structural protein
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PDB id
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1pz8
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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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Modulation of agrin function by alternative splicing and ca2+ binding.
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Authors
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J.Stetefeld,
A.T.Alexandrescu,
M.W.Maciejewski,
M.Jenny,
K.Rathgeb-Szabo,
T.Schulthess,
R.Landwehr,
S.Frank,
M.A.Ruegg,
R.A.Kammerer.
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Ref.
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Structure, 2004,
12,
503-515.
[DOI no: ]
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PubMed id
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Abstract
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The aggregation of acetylcholine receptors on postsynaptic membranes is a key
step in neuromuscular junction development. This process depends on
alternatively spliced forms of the proteoglycan agrin with "B-inserts"
of 8, 11, or 19 residues in the protein's globular C-terminal domain, G3.
Structures of the neural B8 and B11 forms of agrin-G3 were determined by X-ray
crystallography. The structure of G3-B0, which lacks inserts, was determined by
NMR. The agrin-G3 domain adopts a beta jellyroll fold. The B insert site is
flanked by four loops on one edge of the beta sandwich. The loops form a surface
that corresponds to a versatile interaction interface in the family of
structurally related LNS proteins. NMR and X-ray data indicate that this
interaction interface is flexible in agrin-G3 and that flexibility is reduced by
Ca(2+) binding. The plasticity of the interaction interface could enable
different splice forms of agrin to select between multiple binding partners.
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Figure 7.
Figure 7. Comparison of Charge Distribution in Calcium
Bound G Domains(A) The G5 domain of the a2 chain of laminin
(Hohenester et al., 1999). Basic residues important in binding
of a-DG to laminin are labeled green.(B) Calcium-bound NMR
structure of the agrin-G3 B0 domain.(C) Calcium-bound B8 X-ray
structure.(D) Calcium-bound B11 X-ray structure. The calcium
binding site is indicated in the laminin structure, but is left
out for clarity in the agrin structures (conserved red cavity).
The GRASP diagrams were made using the "full.crg" charge/radius
file and are colored according to an electrostatic potential
ramp ranging from +5 e kT -1 (blue, positive) to -5 e kT -1
(red, negative). The calcium ion was not included in
electrostatic calculations. The position of the calcium binding
site (conserved red cavity) is indicated in the laminin
structure.
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The above figure is
reprinted
by permission from Cell Press:
Structure
(2004,
12,
503-515)
copyright 2004.
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