PDBsum entry 4kmh

Protein binding

PDB id: 4kmh

Contents

Protein chains

383 a.a.

Waters ×12

PDB id:

4kmh

Name:

Protein binding

Title:

Crystal structure of suppressor of fused d20

Structure:

Suppressor of fused homolog. Chain: a, b. Fragment: unp residues 1-305, 326-484. Synonym: sufuh. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: sufu, unq650/pro1280. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

3.04Å R-factor: 0.227 R-free: 0.277

Authors:

Y.Zhang,X.Qi,Z.Zhang,G.Wu

Key ref:

Y.Zhang et al. (2013). Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci. Nat Commun, 4, 2608. PubMed id: 24217340 DOI: 10.1038/ncomms3608

Date:

08-May-13 Release date: 20-Nov-13

Protein chains

Q9UMX1  (SUFU_HUMAN) -  Suppressor of fused homolog from Homo sapiens

Seq: 484 a.a.

Struc: 383 a.a.*

* PDB and UniProt seqs differ at 7 residue positions (black crosses)

DOI no: 10.1038/ncomms3608

Nat Commun 4:2608 (2013)

PubMed id: 24217340

Structural insight into the mutual recognition and regulation between Suppressor of Fused and Gli/Ci.

Y.Zhang, L.Fu, X.Qi, Z.Zhang, Y.Xia, J.Jia, J.Jiang, Y.Zhao, G.Wu.

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.