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Originally published In Press as doi:10.1074/jbc.C500423200 on November 14, 2005

J. Biol. Chem., Vol. 281, Issue 1, 13-15, January 6, 2006
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Structure and Carboxyl-terminal Domain (CTD) Binding of the Set2 SRI Domain That Couples Histone H3 Lys36 Methylation to Transcription*{boxs}

Erika Vojnic{ddagger}, Bernd Simon§, Brian D. Strahl¶1, Michael Sattler§2, and Patrick Cramer{ddagger}3

From the {ddagger}Gene Center, Department of Chemistry and Biochemistry, Ludwig-Maximilians-University of Munich, Feodor-Lynen-Strasse 25, 81377 Munich, Germany, the §EMBL, Meyerhofstrasse 1, 69120 Heidelberg, Germany, and the Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599-7260

During mRNA elongation, the SRI domain of the histone H3 methyltransferase Set2 binds to the phosphorylated carboxyl-terminal domain (CTD) of RNA polymerase II. The solution structure of the yeast Set2 SRI domain reveals a novel CTD-binding fold consisting of a left-handed three-helix bundle. NMR titration shows that the SRI domain binds an Ser2/Ser5-phosphorylated CTD peptide comprising two heptapeptide repeats and three flanking NH2-terminal residues, whereas a single CTD repeat is insufficient for binding. Residues that show strong chemical shift perturbations upon CTD binding cluster in two regions. Both CTD tyrosine side chains contact the SRI domain. One of the tyrosines binds in the region with the strongest chemical shift perturbations, formed by the two NH2-terminal helices. Unexpectedly, the SRI domain fold resembles the structure of an RNA polymerase-interacting domain in bacterial {sigma} factors (domain {sigma}2 in {sigma}70).


Received for publication, October 25, 2005 , and in revised form, November 10, 2005.

* This work was supported in part by the Deutsche Forschungsgemeinschaft and the Fonds der Chemischen Industrie. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

{boxs} The on-line version of this article (available at http://www.jbc.org) contains supplemental Table S1 and Figs. S1–S3.

The atomic coordinates and structure factors (code 2C5Z) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).

1 Supported by the National Institutes of Health and is a Pew Scholar in the Biomedical Sciences.

2 To whom correspondence may be addressed. E-mail: sattler{at}embl-heidelberg.de. 3 To whom correspondence may be addressed. Tel.: 49-89-2180-76951; Fax: 49-89-2180-76999; E-mail: cramer{at}LMB.uni-muenchen.de.


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