Open Access System for Information Sharing

Login Library

 

Article
Cited 1 time in webofscience Cited 2 time in scopus
Metadata Downloads

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
Authors
HWANG, CHEOL SANGNGUYEN, KHAKIM, JEONG MOKPark, SE
Date Issued
Mar-2019
Publisher
American Society for Biochemistry and Molecular Biology Inc.
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://oasis.postech.ac.kr/handle/2014.oak/95206
ISSN
0021-9258
Article Type
Article
Citation
Journal of Biological Chemistry, vol. 294, no. 12, page. 4464 - 4476, 2019-03
Files in This Item:
There are no files associated with this item.

qr_code

  • mendeley

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher

 HWANG, CHEOL SANG
Dept of Life Sciences
Read more

Views & Downloads

Browse