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.
Highlights
Cellular pathways involved in determining the fate of essential proteins through post-translational modification events have become an increasingly important area of study [1,2,3,4]
We present a new computational tool known as PupPred, which was constructed to predict the pupylation of prokaryotic proteins by using the latest data of PupDB database [16]
Sequence-derived Hallmarks of Pupylation Sites This investigation focuses on the analysis of ubiquitin-like protein conjugated lysine in prokaryotes
Summary
Cellular pathways involved in determining the fate of essential proteins through post-translational modification events have become an increasingly important area of study [1,2,3,4] Of these modifications, the understanding of eukaryotic ubiquitylation by ubiquitin protein has shown to be especially valuable [5]. Prokaryotic ubiquitin-like protein (Pup) attaches to specific lysine residues of substrate proteins by forming isopeptide bonds to target the proteins for proteasomal degradation in prokaryotes [2,3,4,9] This pathway has been shown to play a particular important role for proteasomal degradation in the prokaryotes [4,9]. Since the proteasomal pathway is critical for both the virulence and persistence of Mtb, identification of the pupylated substrates along with information on the exact sites is fundamental for understanding the pathological mechanisms, and can provide helpful insights into protein degradation in actinomycetes
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