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Three-dimensional structure of the Stat3β homodimer bound to DNA

Abstract

STAT proteins are a family of eukaryotic transcription factors that mediate the response to a large number of cytokines and growth factors. Upon activation by cell-surface receptors or their associated kinases, STAT proteins dimerize, translocate to the nucleus and bind to specific promoter sequences on their target genes. Here we report the first crystal structure of a STAT protein bound to its DNA recognition site at 2.25 Å resolution. The structure provides insight into the various steps by which STAT proteins deliver a response signal directly from the cell membrane to their target genes in the nucleus.

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Figure 1: Structure of STAT proteins.
Figure 3: DNA recognition by the STAT protein.
Figure 2: Ribbon diagram of the Stat3β homodimer–DNA complex.
Figure 4: Binding of the phosphotyrosine peptides by the C-terminal SH2 domains.

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Acknowledgements

We thank our colleagues for their help and for discussions, particularly C. Petosa for help with refinement, A. Perrakis for help with program Sharp, and C. Petosa, F. Baudin, J. Grimes and P.Cramer for comments on the manuscript; we also thank members of the EMBL/ESRF Joint Structural Biology Group, particularly B. Rasmussen, J. Grimes and J. Lescar at ID2, A. Thompson, V. Stojanoff and G. Leonard at BM14, and W. Burmeister and S. Wakatsuki at ID14-3, for their support; and R. Eritja for oligonucleotide synthesis. This project was supported by an institutional fellowship of the European Union and a short-term EMBO fellowship to S.B.

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Correspondence to Christoph W. Müller.

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Becker, S., Groner, B. & Müller, C. Three-dimensional structure of the Stat3β homodimer bound to DNA. Nature 394, 145–151 (1998). https://doi.org/10.1038/28101

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