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Self-association of STAT Proteins from Monomers to Paracrystals

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Jak-Stat Signaling : From Basics to Disease

Abstract

STAT transcription factors assemble dimers of variable solubility and complex conformational dynamics. Unphosphorylated STAT dimers are formed through reciprocal N domain (ND) and core fragment (CF) interactions between protomers, resulting in an antiparallel conformation. Phosphorylated STAT dimers, in contrast, oscillate between this antiparallel and an equally stable parallel conformation that requires reciprocal SH2:pTyr interactions. Moreover, the phosphorylated STAT dimers can polymerize, which occurs both on DNA and off DNA. Polymerization of the parallel phosphodimers is DNA-dependent, and results in cooperative DNA binding, whereas antiparallel phosphodimers can polymerize off DNA, resulting in paracrystals that protect the activated STATs from inactivation. Thus, the central event in cytokine signaling – STAT tyrosine phosphorylation – does not initiate STAT dimerization. Rather, STAT activation regulates the partitioning between different dimer conformations and triggers polymerization of the activated dimers.

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Acknowledgement

The authors would like to thank Dr. N. Wenta for informative discussions and the gifts of purified STAT proteins; and F. Antunes for data collection and figure preparation. This work was supported by grants from Biotechnology and Biological Sciences Research Council (BB/GO019290/1) and Deutsche Forschungsgemeinschaft (UV218/2-3).

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  1. Max Planck Institute of Immunobiology and Epigenetics, Stübeweg 51, 79108, Freiburg, Germany

    Mathias Droescher

  2. School of Biomedical Sciences, Nottingham University Medical School, Nottingham, NG7 2UH, UK

    Uwe Vinkemeier

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Correspondence to Uwe Vinkemeier .

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  1. , Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9/4, Vienna, 1030, Austria

    Thomas Decker

  2. , Animal Breeding and Genetics, University of Vienna, Veterinärplatz 1, Vienna, 1210, Austria

    Mathias Müller

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Droescher, M., Vinkemeier, U. (2012). Self-association of STAT Proteins from Monomers to Paracrystals. In: Decker, T., Müller, M. (eds) Jak-Stat Signaling : From Basics to Disease. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0891-8_4

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