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- Title
Positional proteomics reveals differences in N-terminal proteoform stability.
- Authors
Gawron, Daria; Ndah, Elvis; Gevaert, Kris; Van Damme, Petra
- Abstract
To understand the impact of alternative translation initiation on a proteome, we performed a proteome-wide study on protein turnover using positional proteomics and ribosome profiling to distinguish between N-terminal proteoforms of individual genes. By combining pulsed SILAC with N-terminal COFRADIC, we monitored the stability of 1,941 human N-terminal proteoforms, including 147 N-terminal proteoform pairs that originate from alternative translation initiation, alternative splicing or incomplete processing of the initiator methionine. N-terminally truncated proteoforms were less abundant than canonical proteoforms and often displayed altered stabilities, likely attributed to individual protein characteristics, including intrinsic disorder, but independent of N-terminal amino acid identity or truncation length. We discovered that the removal of initiator methionine by methionine aminopeptidases reduced the stability of processed proteoforms, while susceptibility for N-terminal acetylation did not seem to influence protein turnover rates. Taken together, our findings reveal differences in protein stability between N-terminal proteoforms and point to a role for alternative translation initiation and co-translational initiator methionine removal, next to alternative splicing, in the overall regulation of proteome homeostasis.
- Subjects
METHIONINE; SPATIAL arrangement; PROTEIN stability; RIBOSOME structure; N-terminal residues
- Publication
Molecular Systems Biology, 2016, Vol 12, Issue 2, pn/a
- ISSN
1744-4292
- Publication type
Article
- DOI
10.15252/msb.20156662