PDBsum entry 5e24

Transport/DNA binding/DNA

PDB id: 5e24

Contents

Protein chains

370 a.a.

38 a.a.

424 a.a.

DNA/RNA

Ligands

GLC-GLC-GLC-GLC ×2

EDO ×113

Waters ×669

PDB id:

5e24

Name:

Transport/DNA binding/DNA

Title:

Structure of the su(h)-hairless-DNA repressor complex

Structure:

Maltose-binding periplasmic protein. Chain: a, c. Synonym: mbp,mmbp,maltodextrin-binding protein. Engineered: yes. Mutation: yes. Protein hairless. Chain: b, d. Fragment: unp residues 214-251. Engineered: yes.

Source:

Escherichia coli o157:h7. Organism_taxid: 83334. Gene: male, z5632, ecs5017. Expressed in: escherichia coli. Expression_system_taxid: 562. Drosophila melanogaster. Fruit fly. Organism_taxid: 7227. Gene: h, cg5460.

Resolution:

2.14Å R-factor: 0.174 R-free: 0.193

Authors:

R.A.Kovall,Z.Yuan

Key ref:

Z.Yuan et al. (2016). Structure and Function of the Su(H)-Hairless Repressor Complex, the Major Antagonist of Notch Signaling in Drosophila melanogaster. Plos Biol, 14, e1002509. PubMed id: 27404588 DOI: 10.1371/journal.pbio.1002509

Date:

30-Sep-15 Release date: 15-Jun-16

Protein chains

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

Seq: 396 a.a.

Struc: 370 a.a.*

Protein chains

Q02308  (HLES_DROME) -  Protein hairless from Drosophila melanogaster

Seq: 1077 a.a.

Struc: 38 a.a.

Protein chains

P28159  (SUH_DROME) -  Suppressor of hairless protein from Drosophila melanogaster

Seq: 594 a.a.

Struc: 424 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

DNA/RNA chains

A-A-T-C-T-T-T-C-C-C-A-C-A-G-T 15 bases

T-T-A-C-T-G-T-G-G-G-A-A-A-G-A 15 bases

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F: E.C.?

DOI no: 10.1371/journal.pbio.1002509

Plos Biol 14:e1002509 (2016)

PubMed id: 27404588

Structure and Function of the Su(H)-Hairless Repressor Complex, the Major Antagonist of Notch Signaling in Drosophila melanogaster.

Z.Yuan, H.Praxenthaler, N.Tabaja, R.Torella, A.Preiss, D.Maier, R.A.Kovall.

ABSTRACT

Notch is a conserved signaling pathway that specifies cell fates in metazoans. Receptor-ligand interactions induce changes in gene expression, which is regulated by the transcription factor CBF1/Su(H)/Lag-1 (CSL). CSL interacts with coregulators to repress and activate transcription from Notch target genes. While the molecular details of the activator complex are relatively well understood, the structure-function of CSL-mediated repressor complexes is poorly defined. In Drosophila, the antagonist Hairless directly binds Su(H) (the fly CSL ortholog) to repress transcription from Notch targets. Here, we determine the X-ray structure of the Su(H)-Hairless complex bound to DNA. Hairless binding produces a large conformational change in Su(H) by interacting with residues in the hydrophobic core of Su(H), illustrating the structural plasticity of CSL molecules to interact with different binding partners. Based on the structure, we designed mutants in Hairless and Su(H) that affect binding, but do not affect formation of the activator complex. These mutants were validated in vitro by isothermal titration calorimetry and yeast two- and three-hybrid assays. Moreover, these mutants allowed us to solely characterize the repressor function of Su(H) in vivo.