PDBsum entry 1y1u

Signaling protein

PDB id: 1y1u

Contents

Protein chains

544 a.a. *

* Residue conservation analysis

PDB id:

1y1u

Name:

Signaling protein

Title:

Structure of unphosphorylated stat5a

Structure:

Signal transducer and activator of transcription 5a. Chain: a, b, c. Fragment: stat5a core fragment. Synonym: stat5a, mammary gland factor. Engineered: yes

Source:

Mus musculus. House mouse. Organism_taxid: 10090. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Resolution:

3.21Å R-factor: 0.269 R-free: 0.299

Authors:

D.Neculai,A.M.Neculai,S.Verrier,K.Straub,K.Klumpp,E.Pfitzner,S.Becker

Key ref:

D.Neculai et al. (2005). Structure of the unphosphorylated STAT5a dimer. J Biol Chem, 280, 40782-40787. PubMed id: 16192273 DOI: 10.1074/jbc.M507682200

Date:

19-Nov-04 Release date: 04-Oct-05

Protein chains

P42230  (STA5A_MOUSE) -  Signal transducer and activator of transcription 5A from Mus musculus

Seq: 793 a.a.

Struc: 544 a.a.

DOI no: 10.1074/jbc.M507682200

J Biol Chem 280:40782-40787 (2005)

PubMed id: 16192273

Structure of the unphosphorylated STAT5a dimer.

D.Neculai, A.M.Neculai, S.Verrier, K.Straub, K.Klumpp, E.Pfitzner, S.Becker.

ABSTRACT

STAT proteins have the function of signaling from the cell membrane into the nucleus, where they regulate gene transcription. Latent mammalian STAT proteins can form dimers in the cytoplasm even before receptor-mediated activation by specific tyrosine phosphorylation. Here we describe the 3.21-A crystal structure of an unphosphorylated STAT5a homodimer lacking the N-terminal domain as well as the C-terminal transactivation domain. The overall structure of this fragment is very similar to phosphorylated STATs. However, important differences exist in the dimerization mode. Although the interface between phosphorylated STATs is mediated by their Src-homology 2 domains, the unphosphorylated STAT5a fragment dimerizes in a completely different manner via interactions between their beta-barrel and four-helix bundle domains. The STAT4 N-terminal domain dimer can be docked onto this STAT5a core fragment dimer based on shape and charge complementarities. The separation of the dimeric arrangement, taking place upon activation and nuclear translocation of STAT5a, is demonstrated by fluorescence resonance energy transfer experiments in living cells.

Selected figure(s)

Figure 2.
FIGURE 2. The quality of the electron density allows the identification of intermolecular contacts in the Stat5a dimer. A, 2 mF[o] - DF[c] electron density map contoured at 2 level around the 2-fold axis of the dimer. B, the residues involved in the interactions at the interface are colored according to each monomer after the color coding from Fig. 1B. For clarity only some of them have been labeled. Hydrogen bonds are represented as dashed lines.

Figure 3.
FIGURE 3. Docking model of the N-terminal domain dimer structure of STAT4 onto the dimeric STAT5a core fragment assuming coincidence of their dyads. A, side view of the ensemble. An arrow indicates the dyad. Dashed lines symbolize the missing residues between the C termini of the N-terminal domains and the N termini of the core domains. The color coding for the STAT5a dimer is identical to the one used in Fig. 1A, and the N-terminal domain dimer is colored in cyan. B, electrostatic potential representations of matched surfaces of the docking partners. The common 2-fold axis is indicated by an X, and the complementary surfaces are encircled.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2005, 280, 40782-40787) copyright 2005.

Figures were selected by the author.