Solution NMR structure of MED25(391–543) comprising the activator-interacting domain (ACID) of human mediator subunit 25

  • Alexander Eletsky
  • William T. Ruyechan
  • Rong Xiao
  • Thomas B. Acton
  • Gaetano T. Montelione
  • Thomas Szyperski


The solution NMR structure of protein MED25(391–543), comprising the activator interacting domain (ACID) of subunit 25 of the human mediator, is presented along with the measurement of polypeptide backbone heteronuclear 15N-{1H} NOEs to identify fast internal motional modes. This domain interacts with the acidic transactivation domains of Herpes simplex type 1 (HSV-1) protein VP16 and the Varicella-zoster virus (VZV) major transactivator protein IE62, which initiate transcription of viral genes. The structure is similar to the β-barrel domains of the human protein Ku and the SPOC domain of human protein SHARP, and provides a starting point to understand the structural biology of initiation of HSV-1 and VZV gene activation. Homology models built for the two ACID domains of the prostate tumor overexpressed (PTOV1) protein using the structure of MED25(391–543) as a template suggest that differential biological activities of the ACID domains in MED25 and PTOV1 arise from modulation of quite similar protein–protein interactions by variable residues grouped around highly conserved charged surface areas.


ACID MED25 Mediator complex PTOV Structural genomics 



Activator-interacting domain


CREB-binding protein


Histone deacetylase complex


Herpes simplex virus type 1


Northeast Structural Genomics Consortium


Subunit 25 of the human mediator complex


Nuclear Overhauser effect


Protein Data Bank


Prostate tumor overexpressed


Root mean square deviation


SMRT/HDAC1-associated repressor protein


Spen paralog and ortholog C-terminal domain


Transactivation domain


VP16-binding domain


Varicella-zoster virus



We thank R. Shastry, C. Ciccosanti, H. Janjua, and G.V.T. Swapna for contributions in sample preparation, and J. K. Everett and S. Bhattacharya for helpful discussions. This work was supported by the National Institutes of Health, grant numbers: U54 GM094597 (T.S. and G.T.M.) and R01 AI18449 (W.T.R.). Prof. T. Szyperski is a member of the New York Structural Biology Center. The Center is a STAR center supported by the New York State Office of Science, Technology, and Academic Research. 900 MHz spectrometer was purchased with funds from NIH, USA, the Keck Foundation, New York State, and the NYC Economic Development Corporation. Support was also obtained from the University at Buffalo’s Center for Computational Research.

Supplementary material

10969_2011_9115_MOESM1_ESM.doc (1.1 mb)
Supplementary material 1 (DOC 1170 kb)


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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Alexander Eletsky
    • 1
    • 2
  • William T. Ruyechan
    • 3
    • 4
  • Rong Xiao
    • 5
    • 6
    • 7
  • Thomas B. Acton
    • 5
    • 6
    • 7
  • Gaetano T. Montelione
    • 5
    • 6
    • 7
  • Thomas Szyperski
    • 1
    • 2
  1. 1.Department of ChemistryThe State University of New York at BuffaloBuffaloUSA
  2. 2.Northeast Structural Genomics ConsortiumBuffaloUSA
  3. 3.Department of Microbiology and ImmunologyThe State University of New York at BuffaloBuffaloUSA
  4. 4.Northeast Structural Genomics ConsortiumBuffaloUSA
  5. 5.Center of Advanced Biotechnology and Medicine, Department of Molecular Biology and BiochemistryRutgers, The State University of New JerseyPiscatawayUSA
  6. 6.Department of Biochemistry, Robert Wood Johnson Medical SchoolUniversity of Medicine and Dentistry of New JerseyPiscatawayUSA
  7. 7.Northeast Structural Genomics ConsortiumPiscatawayUSA

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