Format

Send to

Choose Destination
Cell Rep. 2014 Sep 25;8(6):1832-1844. doi: 10.1016/j.celrep.2014.07.055. Epub 2014 Sep 15.

Intrinsically disordered segments affect protein half-life in the cell and during evolution.

Author information

1
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK; Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, 6500 HB Nijmegen, the Netherlands. Electronic address: rvdlee@mrc-lmb.cam.ac.uk.
2
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK.
3
Centre for High-Throughput Biology, University of British Columbia, East Mall, Vancouver BC V6T 1Z4, Canada.
4
Centre for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, 6500 HB Nijmegen, the Netherlands.
5
Department of Molecular Biosciences and Center for Systems and Synthetic Biology, University of Texas at Austin, Austin, TX 78712, USA.
6
MTA-DE Momentum Laboratory of Protein Dynamics, Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen 4032, Hungary.
7
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge CB2 0QH, UK. Electronic address: madanm@mrc-lmb.cam.ac.uk.

Abstract

Precise control of protein turnover is essential for cellular homeostasis. The ubiquitin-proteasome system is well established as a major regulator of protein degradation, but an understanding of how inherent structural features influence the lifetimes of proteins is lacking. We report that yeast, mouse, and human proteins with terminal or internal intrinsically disordered segments have significantly shorter half-lives than proteins without these features. The lengths of the disordered segments that affect protein half-life are compatible with the structure of the proteasome. Divergence in terminal and internal disordered segments in yeast proteins originating from gene duplication leads to significantly altered half-life. Many paralogs that are affected by such changes participate in signaling, where altered protein half-life will directly impact cellular processes and function. Thus, natural variation in the length and position of disordered segments may affect protein half-life and could serve as an underappreciated source of genetic variation with important phenotypic consequences.

PMID:
25220455
PMCID:
PMC4358326
DOI:
10.1016/j.celrep.2014.07.055
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center