Crystal structure of the conserved core of protein arginine methyltransferase PRMT3

Protein arginine methylation has been implicated in signal transduction, nu clear transport and transcription regulation. Protein arginine methyltransf erases (PRMTs) mediate the AdoMet-dependent methylation of many proteins, i ncluding many RNA binding proteins involved in various aspects of RNA proce ssing and/or transport. Here we describe the crystal structure of the rat P RMT3 catalytic core in complex with reaction product AdoIIcy, determined at 2.0 Angstrom resolution. The results reveal a two-domain structure: an Ado Met-binding domain and a barrel-like domain. The AdoMet-binding domain is a compact version of the consensus AdoMet-dependent methyltransferase fold. The active site is situated in a cone-shaped pocket between the two domains . The residues that make up the active site are conserved across the PRMT f amily, consisting of a double-E loop containing two invariant Glu and one H is-Asp proton-relay system. The structure suggests a mechanism for the meth ylation reaction and provides the structural basis for functional character ization of the PRMT family. In addition, crystal packing and solution behav ior suggest dimer formation of the PRMT3 core.