title: Arginyltransferase ATE1 catalyzes midchain arginylation of proteins at side chain carboxylates in vivo.
abstract: Arginylation is an emerging posttranslational modification mediated by Arg-tRNA-protein-transferase (ATE1). It is believed that ATE1 links Arg solely to the N terminus of proteins, requiring prior proteolysis or action by Met-aminopeptidases to expose the arginylated site. Here, we tested the possibility of Arg linkage to midchain sites within intact protein targets and found that many proteins in vivo are modified on the side chains of Asp and Glu by unconventional chemistry that targets the carboxy rather than the amino groups at the target sites. Such arginylation appears to be functionally regulated, and it can be directly mediated by ATE1, in addition to the more conventional ATE1-mediated linkage of Arg to the N-terminal alpha amino group. This midchain arginylation implies an unconventional mechanism of ATE1 action that likely facilitates its major biological role.
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA.
authors: Junling
authors: J
authors: Wang
authors: The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Xuemei
authors: X
authors: Han
authors: The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Catherine C L
authors: CC
authors: Wong
authors: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA.
authors: Hong
authors: H
authors: Cheng
authors: The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Aaron
authors: A
authors: Aslanian
authors: The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Tao
authors: T
authors: Xu
authors: Tufts University School of Medicine, 145 Harrison Avenue, Boston, MA 02111, USA.
authors: Paul
authors: P
authors: Leavis
authors: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA, 19111, USA.
authors: Heinrich
authors: H
authors: Roder
authors: Department of Biology and Department of Chemistry, Brandeis University, 415 South Street, Waltham, MA 02454, USA.
authors: Lizbeth
authors: L
authors: Hedstrom
authors: The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors: John R
authors: JR
authors: Yates
authors: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104, USA. Electronic address: akashina@vet.upenn.edu.
authors: Anna
authors: A
authors: Kashina
mesh_terms: D019881:Aminoacyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000804:Angiotensin II / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry / Q000378:metabolism; D055162:Biocatalysis; D002851:Chromatography, High Pressure Liquid; D018698:Glutamic Acid / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013379:Substrate Specificity
chemical_list: D011994:Recombinant Proteins; D000804:Angiotensin II; D001224:Aspartic Acid; D018698:Glutamic Acid; D019881:Aminoacyltransferases; C019727:arginyltransferase