2a7o

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Template:STRUCTURE 2a7o

Solution Structure of the hSet2/HYPB SRI domain

Overview

The phosphorylation state of the C-terminal repeat domain (CTD) of the largest subunit of RNA polymerase II changes as polymerase transcribes a gene, and the distinct forms of the phospho-CTD (PCTD) recruit different nuclear factors to elongating polymerase. The Set2 histone methyltransferase from yeast was recently shown to bind the PCTD of elongating RNA polymerase II by means of a novel domain termed the Set2-Rpb1 interacting (SRI) domain. Here, we report the solution structure of the SRI domain in human Set2 (hSRI domain), which adopts a left-turned three-helix bundle distinctly different from other structurally characterized PCTD-interacting domains. NMR titration experiments mapped the binding surface of the hSRI domain to helices 1 and 2, and Biacore binding studies showed that the domain binds preferably to [Ser-2 + Ser-5]-phosphorylated CTD peptides containing two or more heptad repeats. Point-mutagenesis studies identified five residues critical for PCTD binding. In view of the differential effects of these point mutations on binding to different CTD phosphopeptides, we propose a model for the hSRI domain interaction with the PCTD.

About this Structure

2A7O is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Solution structure of the Set2-Rpb1 interacting domain of human Set2 and its interaction with the hyperphosphorylated C-terminal domain of Rpb1., Li M, Phatnani HP, Guan Z, Sage H, Greenleaf AL, Zhou P, Proc Natl Acad Sci U S A. 2005 Dec 6;102(49):17636-41. Epub 2005 Nov 28. PMID:16314571 Page seeded by OCA on Sat May 3 18:42:44 2008