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Oligomerization and a distinct tRNA-binding loop are important regulators of human arginyl-transferase function.
Lan, Xin; Huang, Wei; Kim, Su Bin; Fu, Dechen; Abeywansha, Thilini; Lou, Jiemin; Balamurugan, Udayakumaran; Kwon, Yong Tae; Ji, Chang Hoon; Taylor, Derek J; Zhang, Yi.
Afiliación
  • Lan X; Department of Biochemistry, Case Western Reserve University, Cleveland, OH, USA.
  • Huang W; Department of Pharmacology, Case Western Reserve University, Cleveland, OH, USA.
  • Kim SB; Cellular Degradation Biology Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.
  • Fu D; Department of Biochemistry, Case Western Reserve University, Cleveland, OH, USA.
  • Abeywansha T; Department of Biochemistry, Case Western Reserve University, Cleveland, OH, USA.
  • Lou J; Department of Biochemistry, Case Western Reserve University, Cleveland, OH, USA.
  • Balamurugan U; Department of Biochemistry, Case Western Reserve University, Cleveland, OH, USA.
  • Kwon YT; Cellular Degradation Biology Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea.
  • Ji CH; AUTOTAC Bio Inc., Changkkyunggung-ro 254, Jongno-gu, Seoul, Korea.
  • Taylor DJ; Seoul National University Hospital, 71 Daehak ro, Seoul, Republic of Korea.
  • Zhang Y; Cellular Degradation Biology Center and Department of Biomedical Sciences, College of Medicine, Seoul National University, Seoul, Korea. changhoon.ji@snu.ac.kr.
Nat Commun ; 15(1): 6350, 2024 Jul 28.
Article en En | MEDLINE | ID: mdl-39068213
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 tRNAArg, 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aminoaciltransferasas / Multimerización de Proteína Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Aminoaciltransferasas / Multimerización de Proteína Límite: Animals / Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido