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PDBsum entry 1sgf
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Growth factor
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PDB id
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1sgf
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Contents |
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203 a.a.
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109 a.a.
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232 a.a.
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202 a.a.
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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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Structure of mouse 7s ngf: a complex of nerve growth factor with four binding proteins.
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Authors
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B.Bax,
T.L.Blundell,
J.Murray-Rust,
N.Q.Mcdonald.
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Ref.
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Structure, 1997,
5,
1275-1285.
[DOI no: ]
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PubMed id
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Abstract
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BACKGROUND: Nerve growth factor (NGF) is a neurotrophic factor that promotes the
differentiation and survival of certain populations of neurons in the central
and peripheral nervous systems. 7S NGF is an alpha 2 beta 2 gamma 2 complex in
which the beta-NGF dimer (the active neurotrophin) is associated with two
alpha-NGF and two gamma-NGF subunits, which belong to the glandular kallikrein
family of serine proteinases. The gamma-NGF subunit is an active serine
proteinase capable of processing the precursor form of beta-NGF, whereas
alpha-NGF is an inactive serine proteinase. The structure of 7S NGF could be
used as a starting point to design inhibitors that prevent NGF binding to its
receptors, as a potential treatment of neurodegenerative diseases. RESULTS: The
crystal structure of 7S NGF shows that the two gamma-NGF subunits make extensive
interactions with each other around the twofold axis of the complex and have the
C-terminal residues of the beta-NGF subunits bound within their active sites.
The 'activation domain' of each of the alpha-NGF subunits is in an inactive
(zymogen-like) conformation and makes extensive interactions with the beta-NGF
dimer. The two zinc ions that stabilize the complex are located at the
relatively small interfaces between the alpha-NGF and gamma-NGF subunits.
CONCLUSIONS: The structure of 7S NGF shows how the twofold axis of the central
beta-NGF dimer organizes the symmetry of this multisubunit growth factor
complex. The extensive surface of beta-NGF buried within the 7S complex explains
the lack of neurotrophic activity observed for 7S NGF. The regions of the
beta-NGF dimer that contact the alpha-NGF subunits overlap with those known to
engage NGF receptors. Two disulphide-linked loops on alpha-NGF make multiple
interactions with beta-NGF and suggest that it might be possible to design
peptides that inhibit the binding of beta-NGF to its receptors.
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Figure 7.
Figure 7. Electron density surrounding the zinc ion
(off-white sphere) bound between the a1 and g1 subunits. The
final 2F[o] -F[c] map is shown contoured at 1.5s (cyan) and 6s
(off-white).
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The above figure is
reprinted
by permission from Cell Press:
Structure
(1997,
5,
1275-1285)
copyright 1997.
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Secondary reference #1
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Title
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Crystallization and characterization of the high molecular weight form of nerve growth factor (7 s ngf).
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Authors
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N.Q.Mcdonald,
T.L.Blundell.
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Ref.
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J Mol Biol, 1991,
219,
595-601.
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PubMed id
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