PDBsum entry 2a7o

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Transcription PDB id
Protein chain
100 a.a. *
* Residue conservation analysis
PDB id:
Name: Transcription
Title: Solution structure of the hset2/hypb sri domain
Structure: Huntingtin interacting protein b. Chain: a. Fragment: set2 rpb1-interacting (sri) domain, hset2/hybp sri domain, residues 1954-2061. Engineered: yes. Other_details: isoform 1
Source: Homo sapiens. Human. Organism_taxid: 9606. Gene: hset2/hypb. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 20 models
Authors: M.Li,H.P.Phatnani,Z.Guan,H.Sage,A.Greenleaf,P.Zhou
Key ref:
M.Li et al. (2005). 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 U S A, 102, 17636-17641. PubMed id: 16314571 DOI: 10.1073/pnas.0506350102
05-Jul-05     Release date:   01-Nov-05    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9BYW2  (SETD2_HUMAN) -  Histone-lysine N-methyltransferase SETD2
2564 a.a.
100 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure

 Enzyme reactions 
   Enzyme class: E.C.  - Histone-lysine N-methyltransferase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N6-methyl-L-lysine-[histone]
+ L-lysine-[histone]
= S-adenosyl-L-homocysteine
+ N(6)-methyl-L-lysine-[histone]
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     chromosome   1 term 
  Biological process     regulation of transcription, DNA-dependent   2 terms 
  Biochemical function     histone-lysine N-methyltransferase activity     1 term  


    Added reference    
DOI no: 10.1073/pnas.0506350102 Proc Natl Acad Sci U S A 102:17636-17641 (2005)
PubMed id: 16314571  
Solution structure of the Set2-Rpb1 interacting domain of human Set2 and its interaction with the hyperphosphorylated C-terminal domain of Rpb1.
M.Li, H.P.Phatnani, Z.Guan, H.Sage, A.L.Greenleaf, P.Zhou.
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.
  Selected figure(s)  
Figure 1.
Fig. 1. Solution structure and sequence alignment of the hSRI domain. (a) Stereo view of backbone traces from 20 structures of the hSRI domain with helices colored in red and loops in gray. (b) Stereo view of the ribbon diagrams of the hSRI domain. Side chains of conserved hydrophobic residues important for the packing of the three-helix bundle are shown as stick models in green. a and b were prepared by using MOLMOL (35). (c) Sequence alignment of SRI domains from different species (first amino acid of each sequence is numbered). Conserved hydrophobic residues are colored in yellow, basic residues are in blue, and acidic residues are in red. Residues important in maintaining the hydrophobic core of hSRI domain are denoted by green circles above the sequence. Residues important for PCTD interactions are denoted by asterisks. Secondary structures and residue numbers used in NMR studies are shown above the sequence alignment. See Supporting Text for listing of species and GenInfo Identifier (GI) accession numbers.
Figure 3.
Fig. 3. The hSRI domain-PCTD interaction. (a) Biacore sensorgrams showing the interaction of the hSRI domain with different PCTD peptides. The hSRI domain interacts best with [Ser-2 + Ser-5]-phosphorylated PCTDs containing at least two complete repeats (2,5,2,5,2,5 peptide, 2,5,2,5 peptide, and 5,2,5,2 peptide), with severalfold weaker affinity toward 2,5,2 and 5,2,5 peptides (see Table 2) and with extremely weak affinity for other PCTD peptides. (b) Equilibrium binding curves of WT hSRI domain and five single-point mutations that diminish the binding affinity of the hSRI domain toward the 2,5,2,5 PCTD peptide. (c) Surface mapping of the five residues in the hSRI domain important for the PCTD interactions. Orientation of the hSRI domain is identical to that in Fig. 1 a and b. c is generated by MOLMOL (35).
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21792193 Almeida, A.R.Grosso, F.Koch, R.Fenouil, S.Carvalho, J.Andrade, H.Levezinho, M.Gut, D.Eick, I.Gut, J.C.Andrau, P.Ferrier, and M.Carmo-Fonseca (2011).
Splicing enhances recruitment of methyltransferase HYPB/Setd2 and methylation of histone H3 Lys36.
  Nat Struct Mol Biol, 18, 977-983.  
20231364 M.N.Islam, D.Fox, R.Guo, T.Enomoto, and W.Wang (2010).
RecQL5 promotes genome stabilization through two parallel mechanisms--interacting with RNA polymerase II and acting as a helicase.
  Mol Cell Biol, 30, 2460-2472.  
20705653 R.Kanagaraj, D.Huehn, A.MacKellar, M.Menigatti, L.Zheng, V.Urban, I.Shevelev, A.L.Greenleaf, and P.Janscak (2010).
RECQ5 helicase associates with the C-terminal repeat domain of RNA polymerase II during productive elongation phase of transcription.
  Nucleic Acids Res, 38, 8131-8140.  
  20160991 B.R.Donald, and J.Martin (2009).
Automated NMR Assignment and Protein Structure Determination using Sparse Dipolar Coupling Constraints.
  Prog Nucl Magn Reson Spectrosc, 55, 101-127.  
19834511 E.Brookes, and A.Pombo (2009).
Modifications of RNA polymerase II are pivotal in regulating gene expression states.
  EMBO Rep, 10, 1213-1219.  
19711185 J.Zeng, J.Boyles, C.Tripathy, L.Wang, A.Yan, P.Zhou, and B.R.Donald (2009).
High-resolution protein structure determination starting with a global fold calculated from exact solutions to the RDC equations.
  J Biomol NMR, 45, 265-281.
PDB code: 2kiq
19483677 K.Nimura, K.Ura, H.Shiratori, M.Ikawa, M.Okabe, R.J.Schwartz, and Y.Kaneda (2009).
A histone H3 lysine 36 trimethyltransferase links Nkx2-5 to Wolf-Hirschhorn syndrome.
  Nature, 460, 287-291.  
19451231 S.Egloff, H.Al-Rawaf, D.O'Reilly, and S.Murphy (2009).
Chromatin structure is implicated in "late" elongation checkpoints on the U2 snRNA and beta-actin genes.
  Mol Cell Biol, 29, 4002-4013.  
18541663 M.L.Youdell, K.O.Kizer, E.Kisseleva-Romanova, S.M.Fuchs, E.Duro, B.D.Strahl, and J.Mellor (2008).
Roles for Ctk1 and Spt6 in regulating the different methylation states of histone H3 lysine 36.
  Mol Cell Biol, 28, 4915-4926.  
19141475 S.M.Yoh, J.S.Lucas, and K.A.Jones (2008).
The Iws1:Spt6:CTD complex controls cotranscriptional mRNA biosynthesis and HYPB/Setd2-mediated histone H3K36 methylation.
  Genes Dev, 22, 3422-3434.  
17713578 J.A.Armstrong (2007).
Negotiating the nucleosome: factors that allow RNA polymerase II to elongate through chromatin.
  Biochem Cell Biol, 85, 426-434.  
17339332 M.Gullerova, A.Barta, and Z.J.Lorkovic (2007).
Rct1, a nuclear RNA recognition motif-containing cyclophilin, regulates phosphorylation of the RNA polymerase II C-terminal domain.
  Mol Cell Biol, 27, 3601-3611.  
17984971 S.Lall (2007).
Primers on chromatin.
  Nat Struct Mol Biol, 14, 1110-1115.  
16829979 B.T.Seet, I.Dikic, M.M.Zhou, and T.Pawson (2006).
Reading protein modifications with interaction domains.
  Nat Rev Mol Cell Biol, 7, 473-483.  
17125150 R.L.Rich, and D.G.Myszka (2006).
Survey of the year 2005 commercial optical biosensor literature.
  J Mol Recognit, 19, 478-534.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.