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PDBsum entry 3evs
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Cytokine/transferase receptor
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PDB id
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3evs
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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 analysis reveals a spring-Loaded latch as molecular mechanism for gdf-5-Type i receptor specificity.
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Authors
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A.Kotzsch,
J.Nickel,
A.Seher,
W.Sebald,
T.D.Müller.
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Ref.
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Embo J, 2009,
28,
937-947.
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PubMed id
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Abstract
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Dysregulation of growth and differentiation factor 5 (GDF-5) signalling, a
member of the TGF-beta superfamily, is strongly linked to skeletal malformation.
GDF-5-mediated signal transduction involves both BMP type I receptors, BMPR-IA
and BMPR-IB. However, mutations in either GDF-5 or BMPR-IB lead to similar
phenotypes, indicating that in chondrogenesis GDF-5 signalling seems to be
exclusively mediated through BMPR-IB. Here, we present structural insights into
the GDF-5:BMPR-IB complex revealing how binding specificity for BMPR-IB is
generated on a molecular level. In BMPR-IB, a loop within the ligand-binding
epitope functions similar to a latch allowing high-affinity binding of GDF-5. In
BMPR-IA, this latch is in a closed conformation leading to steric repulsion. The
new structural data now provide also a molecular basis of how phenotypically
relevant missense mutations in GDF-5 might impair receptor binding and
activation.
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