title: Solution NMR structure of MED25(391-543) comprising the activator-interacting domain (ACID) of human mediator subunit 25.
abstract: 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.
authors.affiliation: Department of Chemistry, The State University of New York at Buffalo, Buffalo, NY 14260, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Eletsky
authors.forename: William T
authors.initials: WT
authors.lastname: Ruyechan
authors.forename: Rong
authors.initials: R
authors.lastname: Xiao
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Acton
authors.forename: Gaetano T
authors.initials: GT
authors.lastname: Montelione
authors.forename: Thomas
authors.initials: T
authors.lastname: Szyperski
mesh_terms: D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor / Q000737:chemistry; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism; D006801:Humans; D017874:Immediate-Early Proteins / Q000378:metabolism; D056892:Mediator Complex / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular; D011401:Promoter Regions, Genetic; D054730:Protein Interaction Domains and Motifs; D016415:Sequence Alignment; D015534:Trans-Activators / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing
chemical_list: D014408:Biomarkers, Tumor; D017405:Herpes Simplex Virus Protein Vmw65; D017874:Immediate-Early Proteins; D056892:Mediator Complex; D009363:Neoplasm Proteins; D015534:Trans-Activators; D014759:Viral Envelope Proteins; C074221:IE62 protein, Human herpesvirus 3; C483045:MED25 protein, human; C425183:PTOV1 protein, human; D048868:Adaptor Proteins, Signal Transducing