title: Redefining the modular organization of the core Mediator complex.
abstract: The Mediator complex plays an essential role in the regulation of eukaryotic transcription. The Saccharomyces cerevisiae core Mediator comprises 21 subunits, which are organized into Head, Middle and Tail modules. Previously, the Head module was assigned to a distinct dense domain at the base, and the Middle and Tail modules were identified to form a tight structure above the Head module, which apparently contradicted findings from many biochemical and functional studies. Here, we compared the structures of the core Mediator and its subcomplexes, especially the first 3D structure of the Head + Middle modules, which permitted an unambiguous assignment of the three modules. Furthermore, nanogold labeling pinpointing four Mediator subunits from different modules conclusively validated the modular assignment, in which the Head and Middle modules fold back on one another and form the upper portion of the core Mediator, while the Tail module forms a distinct dense domain at the base. The new modular model of the core Mediator has reconciled the previous inconsistencies between the structurally and functionally defined Mediator modules. Collectively, these analyses completely redefine the modular organization of the core Mediator, which allow us to integrate the structural and functional information into a coherent mechanism for the Mediator's modularity and regulation in transcription initiation.
authors.affiliation: School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, China.
authors.forename: Xuejuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Sun
authors.affiliation: School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, China.
authors.forename: Zhenrui
authors.initials: Z
authors.lastname: Ding
authors.affiliation: School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, China.
authors.forename: Jinhua
authors.initials: J
authors.lastname: Ji
authors.affiliation: School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, China.
authors.forename: Jianye
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Kong
authors.affiliation: School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, China.
authors.forename: Jianghong
authors.initials: J
authors.lastname: Yang
authors.affiliation: 1] School of Life Sciences, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, China [2] Hefei National Laboratory for Physical Sciences at the Microscale, Center for Integrative Imaging, 443 Huang-Shan Road, Hefei, Anhui 230027, China [3] Center for Biomedical Engineering, University of Science and Technology of China, 443 Huang-Shan Road, Hefei, Anhui 230027, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Cai
mesh_terms: D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D056892:Mediator Complex / Q000378:metabolism / Q000648:ultrastructure*; D008958:Models, Molecular; D011487:Protein Conformation; D021122:Protein Subunits / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000648:ultrastructure; D012568:Schizosaccharomyces / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins / Q000648:ultrastructure
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C451742:DEF1 protein, S cerevisiae; D056892:Mediator Complex; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins