PDBsum entry 1bgf

Transcription factor

PDB id: 1bgf

Contents

Protein chain

124 a.a. *

Waters ×161

* Residue conservation analysis

PDB id:

1bgf

Name:

Transcription factor

Title:

Stat-4 n-domain

Structure:

Stat-4. Chain: a. Fragment: n-terminal domain. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Biol. unit:

Dimer (from PDB file)

Resolution:

1.45Å R-factor: 0.188 R-free: 0.216

Authors:

U.Vinkemeier,I.Moarefi,J.E.Darnell,J.Kuriyan

Key ref:

U.Vinkemeier et al. (1998). Structure of the amino-terminal protein interaction domain of STAT-4. Science, 279, 1048-1052. PubMed id: 9461439 DOI: 10.1126/science.279.5353.1048

Date:

28-May-98 Release date: 16-Sep-98

Protein chain

P42228  (STAT4_MOUSE) -  Signal transducer and activator of transcription 4 from Mus musculus

Seq: 749 a.a.

Struc: 124 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

DOI no: 10.1126/science.279.5353.1048

Science 279:1048-1052 (1998)

PubMed id: 9461439

Structure of the amino-terminal protein interaction domain of STAT-4.

U.Vinkemeier, I.Moarefi, J.E.Darnell, J.Kuriyan.

ABSTRACT

STATs (signal transducers and activators of transcription) are a family of transcription factors that are specifically activated to regulate gene transcription when cells encounter cytokines and growth factors. The crystal structure of an NH2-terminal conserved domain (N-domain) comprising the first 123 residues of STAT-4 was determined at 1.45 angstroms. The domain consists of eight helices that are assembled into a hook-like structure. The N-domain has been implicated in several protein-protein interactions affecting transcription, and it enables dimerized STAT molecules to polymerize and to bind DNA cooperatively. The structure shows that N-domains can interact through an extensive interface formed by polar interactions across one face of the hook. Mutagenesis of an invariant tryptophan residue at the heart of this interface abolished cooperative DNA binding by the full-length protein in vitro and reduced the transcriptional response after cytokine stimulation in vivo.

Selected figure(s)

Figure 2.
Fig. 2. Tertiary structure of the N-domain of STAT-4. (A) Overall representation of two monomers (green and gray) in the crystallographic^ dimer, viewed approximately orthogonal to the molecular twofold^ axis, which is vertical. The ring-shaped NH[2]-terminal element is colored red in one monomer. (B) Orthogonal view of one^ of the N-domains shown in (A), depicting details of the architecture^ of the ring-shaped element. Side chains that participate in a^ charge-stabilized hydrogen-bond network are shown in a ball-and-stick representation. The side chain and backbone carbonyl of buried^ R31 are shown in magenta. For clarity, the indole ring of the^ invariant residue W4 that seals off this arrangement on the proximal side is drawn with thinner bonds. The blue sphere denotes a buried^ water molecule. Hydrogen bonds are indicated by dotted lines. Oxygen, nitrogen, and carbon atoms are red, blue, and yellow, respectively. Q3-N marks the position of the backbone amide group of residue Q3. The light-red segment of helix 2 highlights its 3[10] helical conformation. Fig. 2 and Fig. 3, B and C were created^ with the program RIBBONS, version 2.0 (28).

Figure 3.
Fig. 3. Structure of the dimer of N-domains. (A) Surface representation of the N-domain dimer indicating the wedge-shaped^ groove and the dimerization interface. Shown are two monomers of a dimer with the left one rotated 90° around the vertical axis away from the original position in the dimer. Note the hook-like^ appearance of the monomer with the coiled-coil of helices 6 and^ 7 pointing out of the planar surface formed by the ring-shaped^ element comprising the NH[2]-terminal 40 residues. Residues from three separate regions of the N-domain make direct or water-mediated^ contacts in the dimer and are color-coded according to their position. Interface residues at the NH[2]-terminus are in green, those in helices 3 and 4 are in blue, and amino acids located in helix 6 are yellow. The position of the critical W37 is highlighted^ in red. The figure was created using GRASP (29). (B) A view at the dimerization interface with amino acids represented^ as ball-and-stick models and the c backbone as a ribbon. The^ monomer is in the same orientation as the one on the right side^ of (A). Side chains are colored as in (A); the backbone ribbon is colored as in Fig. 2B, with the first 40 residues highlighted^ in red. L33 makes a backbone carbonyl group contact, and its position is represented by the filled circle. In the STAT-4 recombinant N-domain used for crystallization, M1 was replaced with G plus four additional small amino acids, one of which (G1) is visible^ in the electron density map. In the crystals, the NH[2]-terminus of G1 is part of the dimer interface, possibly substituting for the native M1. (C) Close-up stereoview of the intermolecular hydrogen-bonding network in the dimer. Selected side chains surrounding the conserved W37 (magenta) in helices 4 and 6 of two monomers (green and gray) are shown. W37 makes direct (E66 ) and water-mediated^ contacts (Q63 ). Water molecules are depicted as blue spheres.

The above figures are reprinted by permission from the AAAs: Science (1998, 279, 1048-1052) copyright 1998.

Figures were selected by an automated process.