2A7O

Solution Structure of the hSet2/HYPB SRI domain

Summary for 2A7O

• Entry DOI: 10.2210/pdb2a7o/pdb
• Descriptor: Huntingtin interacting protein B (1 entity in total)
• Functional Keywords: sri domain, sri, hsri, set2, hset2, phosphoctd associating protein, set2 rpb1-interacting domain, pcid, pcap, transcription
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (Probable): Q9BYW2
• Total number of polymer chains: 1
• Total formula weight: 13147.17

Authors

Li, M.,Phatnani, H.P.,Guan, Z.,Sage, H.,Greenleaf, A.,Zhou, P. (deposition date: 2005-07-05, release date: 2005-11-01, Last modification date: 2024-05-22)

Primary citation

Li, M.,Phatnani, H.P.,Guan, Z.,Sage, H.,Greenleaf, A.,Zhou, P.
Solution structure of the Set2 Rpb1 interacting domain of human Set2 and its interaction with the hyperphosphorylated C-terminal domain of Rpb1
Proc.Natl.Acad.Sci.USA, 102:17636-17641, 2005

PubMed Abstract: 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.

PubMed: 16314571
DOI: 10.1073/pnas.0506350102

Experimental method

SOLUTION NMR