Systematic analysis and prediction of pupylation sites in prokaryotic proteins

PLoS One. 2013 Sep 3;8(9):e74002. doi: 10.1371/journal.pone.0074002. eCollection 2013.

Abstract

Prokaryotic ubiquitin-like protein (Pup) is the first identified prokaryotic protein that is functionally analogous to ubiquitin. Recent studies have shed light on the Pup activation and conjugation to target proteins to be a signal for the selective degradation proteins in Mycobacterium tuberculosis (Mtb). By covalently conjugating the Pup, pupylation functions as a critical post-translational modification (PTM) conserved in actinomycetes. Detecting pupylation sites is crucial and fundamental for understanding the molecular mechanisms of Pup. Yet comparative studies with other PTM suggest that the development of accurate and complete repertories of pupylation is still in its early stages. Unbiased screening for pupylation sites by experimental methods is time consuming and expensive; in silico prediction can provide highly potential candidates and reduce the number of potential candidates that require further in vivo or in vitro confirmation. Here, we present an effective classifier of PupPred for predicting pupylation sites, which shows better performance than existing classifiers. Importantly, this work not only investigates the sequential, structural and evolutionary hallmarks around pupylation sites but also compares the differences of pupylation and ubiquitylation from the environmental, conservative and functional characterization of substrates. These prediction and analysis results may be helpful for further experimental investigation of degradation proteins in prokaryotes. Finally, the PupPred server is available at http://bioinfo.ncu.edu.cn/PupPred.aspx.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Biological Evolution
  • Mycobacterium tuberculosis / metabolism
  • ROC Curve
  • Ubiquitination
  • Ubiquitins / metabolism*

Substances

  • Bacterial Proteins
  • Pup protein, Mycobacterium tuberculosis
  • Ubiquitins

Grant support

This work was supported by the National Natural Science Foundation of China (20605010 and 21175064), and Program for New Century Excellent Talents in University (NCET-11-1002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.