Article
Received: 20 October 2008; Accepted: 19 January 2009
10.1002/pro.83 About DOI
Structural characterization of unphosphorylated STAT5a oligomerization equilibrium in solution by small-angle X-ray scattering |
| Pau Bernadó 1 *, Yolanda Pérez 1, Jascha Blobel 1, Juan Fernández-Recio 2, Dmitri I. Svergun 3 4, Miquel Pons 1 5 * |
| 1Laboratory of Biomolecular NMR, Institute for Research in Biomedicine. Parc Científic de Barcelona, Baldiri Reixac, 10-12, 08028 Barcelona, Spain 2Life Sciences Department, Barcelona Supercomputing Center, Jordi Girona, 31, 08034 Barcelona, Spain 3European Molecular Biology Laboratory, Hamburg Outstation, Notkestrasse 85, 22603 Hamburg, Germany 4European Molecular Institute of Crystallography, Russian Academy of Sciences, Leninsky pr. 59, 117333 Moscow, Russia 5Departament de Química Orgànica, Universitat de Barcelona, Martí i Franquès, 1-11, 08028 Barcelona, Spain |
| email: Pau Bernadó (pau.bernado@irbbarcelona.org) Miquel Pons (mpons@ub.edu) |
*Correspondence to Pau Bernadó, Laboratory of Biomolecular NMR, Institute for Research in Biomedicine. Parc Científic de Barcelona, Baldiri Reixac, 10-12, 08028 Barcelona, Spain
*Correspondence to Miquel Pons, Laboratory of Biomolecular NMR, Institute for Research in Biomedicine. Parc Científic de Barcelona, Baldiri Reixac, 10-12, 08028 Barcelona, Spain
Funded by:
Spanish Ministry of Education-FEDER; Grant Number: BIO2007-63458 EU design study SAXIER; Grant Number: RIDS 011934 Generalitat de Catalunya Spanish Ministry of Education Spanish Ministerio de Educación y Ciencia European Community - Research infrastructure Action under the FP6 
Structuring the European research area program
; Grant Number: RII/2004/5060008
| Keywords |
| STAT proteins signal transduction SAXS oligomeric equilibrium |
| Abstract |
Signal transducer and activator of transcription (STAT) proteins play a crucial role in the activation of gene transcription in response to extracellular stimuli. The regulation and activity of these proteins require a complex rearrangement of the domains. According to the established models, based on crystallographic data, STATs convert from a basal antiparallel inactive dimer into a parallel active one following phosphorylation. The simultaneous analysis of small-angle X-ray scattering data measured at different concentrations of unphosphorylated human STAT5a core domain unambiguously identifies the simultaneous presence of a monomer and a dimer. The dimer is the minor species but could be structurally characterized by SAXS in the presence of the monomer using appropriate computational tools and shown to correspond to the antiparallel assembly. The equilibrium is governed by a moderate dissociation constant of Kd  90  M. Integration of these results with previous knowledge of the N-terminal domain structure and dissociation constants allows the modeling of the full-length protein. A complex network of intermolecular interactions of low or medium affinity is suggested. These contacts can be eventually formed or broken to trigger the dramatic modifications in the dimeric arrangement needed for STAT regulation and activity. |
Received: 20 October 2008; Accepted: 19 January 2009
| Digital Object Identifier (DOI) |
10.1002/pro.83 About DOI
