4KM9

Crystal structure of human Suppressor of Fused

Summary for 4KM9

• Entry DOI: 10.2210/pdb4km9/pdb
• Related: 4KM8 4KMA 4KMD 4KMH
• Descriptor: Suppressor of fused homolog (2 entities in total)
• Functional Keywords: suppressor of fused, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : Q9UMX1
• Total number of polymer chains: 1
• Total formula weight: 54451.07

Authors

Zhang, Y.,Qi, X.,Zhang, Z.,Wu, G. (deposition date: 2013-05-08, release date: 2013-11-20, Last modification date: 2023-11-08)

Primary citation

Zhang, Y.,Fu, L.,Qi, X.,Zhang, Z.,Xia, Y.,Jia, J.,Jiang, J.,Zhao, Y.,Wu, G.
Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci.
Nat Commun, 4:2608-2608, 2013

PubMed Abstract: 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.

PubMed: 24217340
DOI: 10.1038/ncomms3608

Experimental method

X-RAY DIFFRACTION (3.19 Å)