3D24

Crystal structure of ligand-binding domain of estrogen-related receptor alpha (ERRalpha) in complex with the peroxisome proliferators-activated receptor coactivator-1alpha box3 peptide (PGC-1alpha)

3D24 の概要

• エントリーDOI: 10.2210/pdb3d24/pdb
• 関連するPDBエントリー: 1XB7
• 分子名称: Steroid hormone receptor ERR1, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (3 entities in total)
• 機能のキーワード: nuclear receptor, ligand binding domain, coactivator, dna-binding, metal-binding, nucleus, phosphoprotein, transcription, transcription regulation, zinc, zinc-finger, polymorphism, rna-binding, structural genomics, structural proteomics in europe, spine
• 由来する生物種: Homo sapiens; 詳細
• 細胞内の位置: Nucleus: P11474 Q9UBK2
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 60501.74

構造登録者

Moras, D.,Greschik, H.,Flaig, R.,Sato, Y.,Rochel, N.,Structural Proteomics in Europe (SPINE) (登録日: 2008-05-07, 公開日: 2008-06-10, 最終更新日: 2023-08-30)

主引用文献

Greschik, H.,Althage, M.,Flaig, R.,Sato, Y.,Chavant, V.,Peluso-Iltis, C.,Choulier, L.,Cronet, P.,Rochel, N.,Schule, R.,Stromstedt, P.E.,Moras, D.
Communication between the ERR{alpha} Homodimer Interface and the PGC-1{alpha} Binding Surface via the Helix 8-9 Loop.
J.Biol.Chem., 283:20220-20230, 2008

PubMed Abstract: Although structural studies on the ligand-binding domain (LBD) have established the general mode of nuclear receptor (NR)/coactivator interaction, determinants of binding specificity are only partially understood. The LBD of estrogen receptor-alpha (ERalpha), for example, interacts only with a region of peroxisome proliferator-activated receptor coactivator (PGC)-1alpha, which contains the canonical LXXLL motif (NR box2), whereas the LBD of estrogen-related receptor-alpha (ERRalpha) also binds efficiently an untypical, LXXYL-containing region (NR box3) of PGC-1alpha. Surprisingly, in a previous structural study, the ERalpha LBD has been observed to bind NR box3 of transcriptional intermediary factor (TIF)-2 untypically via LXXYL, whereas the ERRalpha LBD binds this region of TIF-2 only poorly. Here we present a new crystal structure of the ERRalpha LBD in complex with a PGC-1alpha box3 peptide. In this structure, residues N-terminal of the PGC-1alpha LXXYL motif formed contacts with helix 4, the loop connecting helices 8 and 9, and with the C terminus of the ERRalpha LBD. Interaction studies using wild-type and mutant PGC-1alpha and ERRalpha showed that these contacts are functionally relevant and are required for efficient ERRalpha/PGC-1alpha interaction. Furthermore, a structure comparison between ERRalpha and ERalpha and mutation analyses provided evidence that the helix 8-9 loop, which differs significantly in both nuclear receptors, is a major determinant of coactivator binding specificity. Finally, our results revealed that in ERRalpha the helix 8-9 loop allosterically links the LBD homodimer interface with the coactivator cleft, thus providing a plausible explanation for distinct PGC-1alpha binding to ERRalpha monomers and homodimers.

PubMed: 18441008
DOI: 10.1074/jbc.M801920200

実験手法

X-RAY DIFFRACTION (2.11 Å)