Structure and TBP binding of the Mediator head subcomplex Med8-Med18-Med20

被引:86
作者
Lariviere, Laurent [1 ]
Geiger, Sebastian [1 ]
Hoeppner, Sabine [1 ]
Roether, Susanne [1 ]
Straesser, Katja [1 ]
Cramer, Patrick [1 ]
机构
[1] Univ Munich, Dept Chem & Biochem, D-81377 Munich, Germany
关键词
D O I
10.1038/nsmb1143
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The Mediator head module stimulates basal RNA polymerase II (Pol II) transcription and enables transcriptional regulation. Here we show that the head subunits Med8, Med18 and Med20 form a subcomplex (Med8/18/20) with two submodules. The highly conserved N-terminal domain of Med8 forms one submodule that binds the TATA box-binding protein (TBP) in vitro and is essential in vivo. The second submodule consists of the C-terminal region of Med8 (Med8C), Med18 and Med20. X-ray analysis of this submodule reveals that Med18 and Med20 form related beta-barrel folds. A conserved putative protein-interaction face on the Med8C/18/20 submodule includes sites altered by srb mutations, which counteract defects resulting from Pol II truncation. Our results and published data support a positive role of the Med8/18/20 subcomplex in initiation-complex formation and suggest that the Mediator head contains a multipartite TBP-binding site that can be modulated by transcriptional activators.
引用
收藏
页码:895 / 901
页数:7
相关论文
共 49 条
[1]   Genome-wide location of the coactivator mediator: Binding without activation and transient Cdk8 interaction on DNA [J].
Andrau, JC ;
van de Pasch, L ;
Lijnzaad, P ;
Bijma, T ;
Koerkamp, MG ;
van de Peppel, J ;
Werner, M ;
Holstege, FCP .
MOLECULAR CELL, 2006, 22 (02) :179-192
[2]   Architecture of initiation-competent 12-subunit RNA polymerase II [J].
Armache, KJ ;
Kettenberger, H ;
Cramer, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (12) :6964-6968
[3]   THE CCP4 SUITE - PROGRAMS FOR PROTEIN CRYSTALLOGRAPHY [J].
BAILEY, S .
ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY, 1994, 50 :760-763
[4]   A conserved mediator hinge revealed in the structure of the MED7•MED21 (Med7•Srb7) heterodimer [J].
Baumli, S ;
Hoeppner, S ;
Cramer, P .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (18) :18171-18178
[5]  
Björklund S, 2004, ADV PROTEIN CHEM, V67, P43
[6]   Evidence for a mediator of RNA polymerase II transcriptional regulation conserved from yeast to man [J].
Boube, M ;
Joulia, L ;
Cribbs, DL ;
Bourbon, HM .
CELL, 2002, 110 (02) :143-151
[7]   A unified nomenclature for protein subunits of Mediator complexes linking transcriptional regulators to RNA polymerase II [J].
Bourbon, HM ;
Aguilera, A ;
Ansari, AZ ;
Asturias, FJ ;
Berk, AJ ;
Bjorklund, S ;
Blackwell, TK ;
Borggrefe, T ;
Carey, M ;
Carlson, M ;
Conaway, JW ;
Conaway, RC ;
Emmons, SW ;
Fondell, JD ;
Freedman, LP ;
Fukasawa, T ;
Gustafsson, CM ;
Han, M ;
He, X ;
Herman, PK ;
Hinnebusch, AG ;
Holmberg, S ;
Holstege, FC ;
Jaehning, JA ;
Kim, YJ ;
Kuras, L ;
Leutz, A ;
Lis, JT ;
Meisterernest, M ;
Naar, AM ;
Nasmyth, K ;
Parvin, JD ;
Ptashne, M ;
Reinberg, D ;
Ronne, H ;
Sadowski, I ;
Sakurai, H ;
Sipiczki, M ;
Sternberg, PW ;
Stillman, DJ ;
Strich, R ;
Struhl, K ;
Svejstrup, JQ ;
Tuck, S ;
Winston, F ;
Roeder, RG ;
Kornberg, RD .
MOLECULAR CELL, 2004, 14 (05) :553-557
[8]   Mammalian mediator subunit mMED8 is an Elongin BC-interacting protein that can assemble with Cul2 and Rbx1 to reconstitute a ubiquitin ligase [J].
Brower, CS ;
Sato, S ;
Tomomori-Sato, C ;
Kamura, T ;
Pause, A ;
Stearman, R ;
Klausner, RD ;
Malik, S ;
Lane, WS ;
Sorokina, I ;
Roeder, RG ;
Conaway, JW ;
Conaway, RC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (16) :10353-10358
[9]  
Brunger AT, 1998, ACTA CRYSTALLOGR D, V54, P905, DOI 10.1107/s0907444998003254
[10]  
BUDISA N, 1995, EUR J BIOCHEM, V230, P788