NMR structure of the human Mediator MED25 ACID domain.
MED25 (ARC92/ACID1) is a 747 residues subunit specific to higher eukaryote Mediator complex, an essential component of the RNA polymerase II general transcriptional machinery. MED25 is a target of the Herpes simplex virus transactivator protein VP16. MED25 interacts with VP16 through a central MED25 PTOV (Prostate tumour overexpressed)/ACID (Activator interacting domain) domain of unknown structure. As a first step towards understanding the mechanism of recruitment of transactivation domains by MED25, we report here the NMR structure of the MED25 ACID domain. The domain architecture consists of a closed β-barrel with seven strands (Β1-Β7) and three α-helices (H1-H3), an architecture showing similarities to that of the SPOC (Spen paralog and ortholog C-terminal domain) domain-like superfamily. Preliminary NMR chemical shift mapping showed that VP16 H2 (VP16C) interacts with MED25 ACID through one face of the β-barrel, defined by strands B4-B7-B6.
Bontems
François
F
CNRS UPR 2301, Chimie et biochimie structurales, Institut de Chimie des Substances Naturelles, Centre de recherche de Gif-sur-Yvette, 91190 Gif-sur-Yvette, France.
Verger
Alexis
A
Dewitte
Frédérique
F
Lens
Zoé
Z
Baert
Jean-Luc
JL
Ferreira
Elisabeth
E
de Launoit
Yvan
Y
Sizun
Christina
C
Guittet
Eric
E
Villeret
Vincent
V
Monté
Didier
D
D000595:Amino Acid Sequence; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D006801:Humans; D056892:Mediator Complex / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
D017405:Herpes Simplex Virus Protein Vmw65; C483045:MED25 protein, human; D056892:Mediator Complex