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

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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 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.