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

J Struct Funct Genomics. 2011 Sep;12(3):159-66. doi: 10.1007/s10969-011-9115-1. Epub 2011 Jul 23.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biomarkers, Tumor / chemistry
  • Herpes Simplex Virus Protein Vmw65 / metabolism
  • Humans
  • Immediate-Early Proteins / metabolism
  • Mediator Complex / chemistry*
  • Mediator Complex / genetics
  • Mediator Complex / metabolism
  • Molecular Sequence Data
  • Neoplasm Proteins / chemistry
  • Nuclear Magnetic Resonance, Biomolecular
  • Promoter Regions, Genetic
  • Protein Interaction Domains and Motifs
  • Sequence Alignment
  • Trans-Activators / metabolism
  • Viral Envelope Proteins / metabolism


  • Biomarkers, Tumor
  • Herpes Simplex Virus Protein Vmw65
  • IE62 protein, Human herpesvirus 3
  • Immediate-Early Proteins
  • MED25 protein, human
  • Mediator Complex
  • Neoplasm Proteins
  • PTOV1 protein, human
  • Trans-Activators
  • Viral Envelope Proteins