title: Functional insights from structures of coactivator-associated arginine methyltransferase 1 domains.
abstract: 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 A 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 A, 2.4 A and 2.2 A, 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.
authors: Département de Biologie et Génomique Structurales, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire), UMR 7104 CNRS, U596 INSERM, ULP, Illkirch, France.
authors: Nathalie
authors: N
authors: Troffer-Charlier
authors: Vincent
authors: V
authors: Cura
authors: Pierre
authors: P
authors: Hassenboehler
authors: Dino
authors: D
authors: Moras
authors: Jean
authors: J
authors: Cavarelli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002467:Cell Nucleus / Q000378:metabolism; D018360:Crystallography, X-Ray; D006801:Humans; D051379:Mice; D008957:Models, Genetic; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry* / Q000502:physiology*; D051381:Rats; D017386:Sequence Homology, Amino Acid
chemical_list: D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1