title: Crystal structure of Legionella pneumophila type IV secretion system effector LegAS4.
abstract: The SET domain of LegAS4, a type IV secretion system effector of Legionella pneumophila, is a eukaryotic protein motif involved in histone methylation and epigenetic modulation. The SET domain of LegAS4 is involved in the modification of Lys4 of histone H3 (H3K4) in the nucleolus of the host cell, thereby enhancing heterochromatic rDNA transcription. Moreover, LegAS4 contains an ankyrin repeat domain of unknown function at its C-terminal region. Here, we report the crystal structure of LegAS4 in complex with S-adenosyl-l-methionine (SAM). Our data indicate that the ankyrin repeats interact extensively with the SET domain, especially with the SAM-binding amino acids, through conserved residues. Conserved surface analysis marks Glu159, Glu203, and Glu206 on the SET domain serve as candidate residues involved in interaction with the positively charged histone tail. Conserved surface residues on the ankyrin repeat domain surround a small pocket, which is suspected to serve as a binding site for an unknown ligand.
authors: Division of Biotechnology, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, Republic of Korea.
authors: Jonghyeon
authors: J
authors: Son
authors: Division of Biotechnology, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, Republic of Korea.
authors: Chang Hwa
authors: CH
authors: Jo
authors: Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Chung-Buk 363-883, Republic of Korea.
authors: Ravichandran N
authors: RN
authors: Murugan
authors: Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Chung-Buk 363-883, Republic of Korea.
authors: Jeong Kyu
authors: JK
authors: Bang
authors: Division of Biotechnology, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, Republic of Korea. Electronic address: chahong@korea.ac.kr.
authors: Kwang Yeon
authors: KY
authors: Hwang
authors: Division of Biotechnology, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, Republic of Korea; Institute of Life Science and Natural Resources, Korea University, Seoul 136-713, Republic of Korea. Electronic address: dreadco@gmail.com.
authors: Woo Cheol
authors: WC
authors: Lee
mesh_terms: D000595:Amino Acid Sequence; D017089:Ankyrin Repeat; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006657:Histones / Q000235:genetics / Q000378:metabolism; D016952:Legionella pneumophila / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054730:Protein Interaction Domains and Motifs; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000737:chemistry / Q000378:metabolism; D040681:Structural Homology, Protein; D000069319:Type IV Secretion Systems / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D006657:Histones; D011994:Recombinant Proteins; D000069319:Type IV Secretion Systems; D012436:S-Adenosylmethionine
keywords: Ankyrin repeat; LegAS4; Legionella pneumophila; RomA; SET domain