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N-terminal methionine excision of proteins creates tertiary destabilizing N-degrons of the Arg/N-end rule pathway

Title
N-terminal methionine excision of proteins creates tertiary destabilizing N-degrons of the Arg/N-end rule pathway
Author
김정목
Keywords
ubiquitin; ubiquitin ligase; protein degradation; proteasome; acetylation; N-end rule; N-terminal acetylation; N-terminal amidase; N-terminal arginylation; N-terminal methionine excision
Issue Date
2019-03
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v. 294, NO 12, Page. 4464-4476
Abstract
All organisms begin protein synthesis with methionine (Met). The resulting initiator Met of nascent proteins is irreversibly processed by Met aminopeptidases (MetAPs). N-terminal (Nt) Met excision (NME) is an evolutionarily conserved and essential process operating on up to two-thirds of proteins. However, the universal function of NME remains largely unknown. MetAPs have a well-known processing preference for Nt-Met with Ala, Ser, Gly, Thr, Cys, Pro, or Val at position 2, but using CHX-chase assays to assess protein degradation in yeast cells, as well as protein-binding and RT-qPCR assays, we demonstrate here that NME also occurs on nascent proteins bearing Met-Asn or Met-Gln at their N termini. We found that the NME at these termini exposes the tertiary destabilizing Nt residues (Asn or Gln) of the Arg/N-end rule pathway, which degrades proteins according to the composition of their Nt residues. We also identified a yeast DNA repair protein, MQ-Rad16, bearing a Met-Gln N terminus, as well as a human tropomyosin-receptor kinase-fused gene (TFG) protein, MN-TFG, bearing a Met-Asn N terminus as physiological, MetAP-processed Arg/N-end rule substrates. Furthermore, we show that the loss of the components of the Arg/N-end rule pathway substantially suppresses the growth defects of naa20 yeast cells lacking the catalytic subunit of NatB Nt acetylase at 37 degrees C. Collectively, the results of our study reveal that NME is a key upstream step for the creation of the Arg/N-end rule substrates bearing tertiary destabilizing residues in vivo.
URI
http://www.jbc.org/content/294/12/4464http://repository.hanyang.ac.kr/handle/20.500.11754/110958
ISSN
1083-351X
DOI
10.1074/jbc.RA118.006913
Appears in Collections:
COLLEGE OF NATURAL SCIENCES[S](자연과학대학) > LIFE SCIENCE(생명과학과) > Articles
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