Crystal Structure of the Plant Epigenetic Protein Arginine Methyltransferase 10

• Published in: Journal of molecular biology 2011-11, Vol.414 (1), p.106-122
• Main Authors: Cheng, Yuan, Frazier, Monica, Lu, Falong, Cao, Xiaofeng, Redinbo, Matthew R.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; amino acid sequences; Arabidopsis; Arabidopsis - metabolism; Arabidopsis Proteins; Arabidopsis Proteins - chemistry; Arabidopsis Proteins - metabolism; Arabidopsis thaliana; Catalytic Domain; chemistry; Crystal structure; Crystallography, X-Ray; dimerization; enzyme activity; epigenetics; flowering time; metabolism; Methylation; methyltransferases; Methyltransferases - chemistry; Methyltransferases - metabolism; Models, Molecular; molecular dynamics; Molecular Dynamics Simulation; Molecular Sequence Data; Protein Conformation; protein motion; Protein Multimerization; protein structure; Protein Structure, Secondary; S-Adenosylhomocysteine; S-Adenosylhomocysteine - chemistry; S-Adenosylhomocysteine - metabolism; Sequence Homology, Amino Acid; Substrate Specificity
• ISSN: 0022-2836; 1089-8638
• DOI: 10.1016/j.jmb.2011.09.040

Protein arginine methyltransferase 10 (PRMT10) is a type I arginine methyltransferase that is essential for regulating flowering time in Arabidopsis thaliana. We present a 2.6 Å resolution crystal structure of A. thaliana PRMT 10 (AtPRMT10) in complex with a reaction product, S-adenosylhomocysteine. The structure reveals a dimerization arm that is 12–20 residues longer than PRMT structures elucidated previously; as a result, the essential AtPRMT10 dimer exhibits a large central cavity and a distinctly accessible active site. We employ molecular dynamics to examine how dimerization facilitates AtPRMT10 motions necessary for activity, and we show that these motions are conserved in other PRMT enzymes. Finally, functional data reveal that the 10 N-terminal residues of AtPRMT10 influence substrate specificity, and that enzyme activity is dependent on substrate protein sequences distal from the methylation site. Taken together, these data provide insights into the molecular mechanism of AtPRMT10, as well as other members of the PRMT family of enzymes. They highlight differences between AtPRMT10 and other PRMTs but also indicate that motions are a conserved element of PRMT function. [Display omitted] ► AtPRMT10 is required for epigenetic control of flowering time. ► The AtPRMT10 crystal structure is the first crystal structure of a plant PRMT. ► The structure exhibits a uniquely open conformation relative to other PRMTs. ► Functional data establish distinct features of AtPRMT10. ► Molecular dynamics data identify conserved motions in the PRMT family.