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PDBsum entry 4kmh
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Protein binding
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PDB id
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4kmh
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References listed in PDB file
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Key reference
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Title
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Structural insight into the mutual recognition and regulation between suppressor of fused and gli/ci.
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Authors
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Y.Zhang,
L.Fu,
X.Qi,
Z.Zhang,
Y.Xia,
J.Jia,
J.Jiang,
Y.Zhao,
G.Wu.
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Ref.
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Nat Commun, 2013,
4,
2608.
[DOI no: ]
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PubMed id
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Abstract
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Hedgehog (Hh) signalling regulates embryonic development and adult tissue
homoeostasis. Mutations of its pathway components including Suppressor of Fused
(Sufu) and Gli/Ci predispose to cancers and congenital anomalies. The Sufu-Gli
protein complex occupies a central position in the vertebrate Hh signalling
pathway, especially in mammals. Here structures of full-length human and
Drosophila Sufu, the human Sufu-Gli complex, along with normal mode analysis and
FRET measurement results, reveal that Sufu alternates between 'open' and
'closed' conformations. The 'closed' form of Sufu is stabilized by Gli binding
and inhibited by Hh treatment, whereas the 'open' state of Sufu is promoted by
Gli-dissociation and Hh signalling. Mutations of critical interface residues
disrupt the Sufu-Gli complex and prevent Sufu from repressing Gli-mediated
transcription, tethering Gli in the cytoplasm and protecting Gli from the 26S
proteasome-mediated degradation. Our study thus provides mechanistic insight
into the mutual recognition and regulation between Sufu and Gli/Ci.
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