지창훈 (서울대학교 세포분해생물학센터 / (주)오토텍바이오)

한빛사논문

조회174

서울대학교 세포분해생물학센터 / (주)오토텍바이오

CV File 477 kb

Nat. Commun., Jul 28 2024, 15 (1) | https://doi.org/10.1038/s41467-024-50719-w Oligomerization and a distinct tRNA-binding loop are important regulators of human arginyl-transferase function

Xin Lan^1,7, Wei Huang^2,7, Su Bin Kim^3,7, Dechen Fu¹, Thilini Abeywansha¹, Jiemin Lou¹, Udayakumaran Balamurugan¹, Yong Tae Kwon^3,4,5, Chang Hoon Ji^3,4,8, Derek J. Taylor^1,2,6,8& Yi Zhang^1,6,8

¹Department of Biochemistry, Case Western Reserve University, Cleveland, OH, USA.

²Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.

³Cellular Degradation Biology Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.

⁴AUTOTAC Bio Inc., Changkkyunggung-ro 254, Jongno-gu, Seoul, Korea.

⁵Seoul National University Hospital, 71 Daehak ro, Seoul, Republic of Korea.

⁶Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH, USA.

⁷These authors contributed equally: Xin Lan, Wei Huang, Su Bin Kim.

⁸These authors jointly supervised this work: Chang Hoon Ji, Derek J. Taylor, Yi Zhang

Corresponding authors

Correspondence to Chang Hoon Ji, Derek J. Taylor or Yi Zhang.

Abstract

The arginyl-transferase ATE1 is a tRNA-dependent enzyme that covalently attaches an arginine molecule to a protein substrate. Conserved from yeast to humans, ATE1 deficiency in mice correlates with defects in cardiovascular development and angiogenesis and results in embryonic lethality, while conditional knockouts exhibit reproductive, developmental, and neurological deficiencies. Despite the recent revelation of the tRNA binding mechanism and the catalytic cycle of yeast ATE1, the structure-function relationship of ATE1 in higher organisms is not well understood. In this study, we present the three-dimensional structure of human ATE1 in an apo-state and in complex with its tRNA cofactor and a peptide substrate. In contrast to its yeast counterpart, human ATE1 forms a symmetric homodimer, which dissociates upon binding of a substrate. Furthermore, human ATE1 includes a unique and extended loop that wraps around tRNA^Arg, creating extensive contacts with the T-arm of the tRNA cofactor. Substituting key residues identified in the substrate binding site of ATE1 abolishes enzymatic activity and results in the accumulation of ATE1 substrates in cells.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-31)
연구진국내(교신)+국외 연구진
분야 생명과학 > 세포생물학

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