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PDBsum entry 4ht1
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Immune system
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PDB id
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4ht1
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Contents |
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131 a.a.
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210 a.a.
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217 a.a.
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PDB id:
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| Name: |
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Immune system
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Title:
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Human tweak in complex with the fab fragment of a neutralizing antibody
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Structure:
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Tumor necrosis factor ligand superfamily member 12. Chain: t. Synonym: apo3 ligand, tnf-related weak inducer of apoptosis, tweak, tumor necrosis factor ligand superfamily member 12, membrane form, tumor necrosis factor ligand superfamily member 12, secreted form. Chimeric antibody fab. Chain: h. Chimeric antibody fab. Chain: l
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Source:
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Homo sapiens. Human. Organism_taxid: 9606. Oryctolagus cuniculus. Organism_taxid: 9986. Other_details: chimeric antibody. Other_details: chimeric antibody
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Resolution:
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2.50Å
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R-factor:
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0.188
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R-free:
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0.211
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Authors:
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A.Lammens
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Key ref:
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A.Lammens
et al.
(2013).
Crystal structure of human TWEAK in complex with the Fab fragment of a neutralizing antibody reveals insights into receptor binding.
Plos One,
8,
e62697.
PubMed id:
DOI:
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Date:
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31-Oct-12
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Release date:
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12-Jun-13
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PROCHECK
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Headers
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References
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O43508
(TNF12_HUMAN) -
Tumor necrosis factor ligand superfamily member 12 from Homo sapiens
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Seq:
Struc:
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249 a.a.
131 a.a.
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DOI no:
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Plos One
8:e62697
(2013)
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PubMed id:
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Crystal structure of human TWEAK in complex with the Fab fragment of a neutralizing antibody reveals insights into receptor binding.
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A.Lammens,
M.Baehner,
U.Kohnert,
J.Niewoehner,
L.von Proff,
M.Schraeml,
K.Lammens,
K.P.Hopfner.
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ABSTRACT
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The tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a
multifunctional cytokine playing a key role in tissue regeneration and
remodeling. Dysregulation of TWEAK signaling is involved in various pathological
processes like autoimmune diseases and cancer. The unique interaction with its
cognate receptor Fn14 makes both ligand and receptor promising targets for novel
therapeutics. To gain insights into this important signaling pathway, we
determined the structure of soluble human TWEAK in complex with the Fab fragment
of an antibody selected for inhibition of receptor binding. In the crystallized
complex TWEAK is bound by three Fab fragments of the neutralizing antibody.
Homology modeling shows that Fab binding overlaps with the putative Fn14 binding
site of TWEAK. Docking of the Fn14 cysteine rich domain (CRD) to that site
generates a highly complementary interface with perfectly opposing charged and
hydrophobic residues. Taken together the presented structure provides new
insights into the biology of TWEAK and the TWEAK/Fn14 pathway, which will help
to optimize the therapeutic strategy for treatment of related cancer types and
autoimmune diseases.
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Links
