title: A flexible cofactor-binding loop in the novel arginine methyltransferase Sfm1.
abstract: Arginine methylation is a common post-translational modification and is critical for many cellular processes. Sfm1 is a novel arginine methyltransferase that contains a SpoU-TrmD (SPOUT) domain, a typical fold known for RNA methylation, but acts on a ribosomal protein. The underlying mechanism is poorly understood. Here, we report cocrystal structures of Sfm1 in complex with various ligands. We found that a critical loop responsible for S-adenosyl-l-methionine (SAM) binding adopts a different conformation from previous reports, and SAM appears to exhibit double conformations. Deletion of this loop greatly reduces the affinity of Sfm1 to SAM. Additionally, by comparison to closely related tRNA-methyltransferase Trm10, our structural analyses offer a good explanation why the two enzymes utilize distinct substrates, providing insights into the molecular mechanism.
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, Guangzhou, China.|Center for Cellular & Structural biology, The Sun Yat-Sen University, Guangzhou, China.
authors.forename: Caiyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, Guangzhou, China.|Center for Cellular & Structural biology, The Sun Yat-Sen University, Guangzhou, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory for Biocontrol, School of Life Sciences, The Sun Yat-Sen University, Guangzhou, China.|Center for Cellular & Structural biology, The Sun Yat-Sen University, Guangzhou, China.
authors.forename: Wei
authors.identifier: 0000-0003-2410-2135
authors.initials: W
authors.lastname: Xie
mesh_terms: D000595:Amino Acid Sequence; D020134:Catalytic Domain; D003067:Coenzymes / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D017433:Protein Structure, Secondary; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry* / Q000378:metabolism*; D012436:S-Adenosylmethionine / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D040681:Structural Homology, Protein
chemical_list: D003067:Coenzymes; D029701:Saccharomyces cerevisiae Proteins; D012436:S-Adenosylmethionine; D011484:Protein-Arginine N-Methyltransferases; C000618499:Sfm1 protein, S cerevisiae
keywords: S-adenosine-l-methionine; Sfm1; arginine methyltransferase