PDBsum entry 4bl8

Signaling protein

PDB id: 4bl8

Contents

Protein chains

727 a.a.

Ligands

GLC-GLC ×2

PDB id:

4bl8

Name:

Signaling protein

Title:

Crystal structure of full-length human suppressor of fused (sufu)

Structure:

Maltose-binding periplasmic protein, suppressor of fused homolog. Chain: a, b. Fragment: mbpp residues 29-387,sufuh residues 32-278,361-483. Engineered: yes. Mutation: yes

Source:

Escherichia coli, homo sapiens. Organism_taxid: 562, 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: jm109(de3).

Resolution:

3.04Å R-factor: 0.203 R-free: 0.247

Authors:

M.Karlstrom,C.Finta,A.L.Cherry,R.Toftgard,L.Jovine

Key ref:

A.L.Cherry et al. (2013). Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation. Acta Crystallogr D Biol Crystallogr, 69, 2563-2579. PubMed id: 24311597 DOI: 10.1107/S0907444913028473

Date:

02-May-13 Release date: 27-Nov-13

Protein chains

P0AEX9  (MALE_ECOLI) -  Maltose/maltodextrin-binding periplasmic protein from Escherichia coli (strain K12)

Seq: 396 a.a.

Struc: 727 a.a.*

Protein chains

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

Seq: 484 a.a.

Struc: 727 a.a.*

* PDB and UniProt seqs differ at 36 residue positions (black crosses)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1107/S0907444913028473

Acta Crystallogr D Biol Crystallogr 69:2563-2579 (2013)

PubMed id: 24311597

Structural basis of SUFU-GLI interaction in human Hedgehog signalling regulation.

A.L.Cherry, C.Finta, M.Karlström, Q.Jin, T.Schwend, J.Astorga-Wells, R.A.Zubarev, M.Del Campo, A.R.Criswell, D.de Sanctis, L.Jovine, R.Toftgård.

ABSTRACT

Hedgehog signalling plays a fundamental role in the control of metazoan development, cell proliferation and differentiation, as highlighted by the fact that its deregulation is associated with the development of many human tumours. SUFU is an essential intracellular negative regulator of mammalian Hedgehog signalling and acts by binding and modulating the activity of GLI transcription factors. Despite its central importance, little is known about SUFU regulation and the nature of SUFU-GLI interaction. Here, the crystal and small-angle X-ray scattering structures of full-length human SUFU and its complex with the key SYGHL motif conserved in all GLIs are reported. It is demonstrated that GLI binding is associated with major conformational changes in SUFU, including an intrinsically disordered loop that is also crucial for pathway activation. These findings reveal the structure of the SUFU-GLI interface and suggest a mechanism for an essential regulatory step in Hedgehog signalling, offering possibilities for the development of novel pathway modulators and therapeutics.