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Article

  • The EMBO Journal (2007) 26, 4391 - 4401
  • doi:10.1038/sj.emboj.7601855

Published online: 20 September 2007

Functional insights from structures of coactivator-associated arginine methyltransferase 1 domains

Nathalie Troffer-Charlier1,a, Vincent Cura1,a, Pierre Hassenboehler1, Dino Moras1 and Jean Cavarelli1

  1. Département de Biologie et Génomique Structurales, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) (UMR 7104 CNRS, U596 INSERM, ULP), Illkirch, France

Correspondence to:

Jean Cavarelli, Laboratoire de Biologie et Génomique Structurales, IGBMC (CNRS/INSERM/ULP), 1 rue Laurent Fries, BP 10142, Ilkirch 67404, France. Tel.: +33 388 65 5793; Fax: +33 388 65 3276; E-mail: cava@igbmc.u-strasbg.fr

aThese authors contributed equally to this work

Received 11 June 2007; Accepted 21 August 2007

Coactivator-associated arginine methyltransferase 1 (CARM1), a protein arginine methyltransferase recruited by several transcription factors, methylates a large variety of proteins and plays a critical role in gene expression. We report, in this paper, four crystal structures of isolated modules of CARM1. The 1.7 Å crystal structure of the N-terminal domain of CARM1 reveals an unexpected PH domain, a scaffold frequently found to regulate protein–protein interactions in a large variety of biological processes. Three crystal structures of the CARM1 catalytic module, two free and one cofactor-bound forms (refined at 2.55 Å, 2.4 Å and 2.2 Å, respectively) reveal large structural modifications including disorder to order transition, helix to strand transition and active site modifications. The N-terminal and the C-terminal end of CARM1 catalytic module contain molecular switches that may inspire how CARM1 regulates its biological activities by protein–protein interactions.

  • Keywords:

    • CARM1,
    • coactivator-associated arginine methyltransferase 1,
    • nuclear receptor coactivator,
    • PRMT,
    • protein ariginine methylation