Abstract
BackgroundThe identification of charge clusters (runs of charged residues) in proteins and their mapping within the protein structure sequence is an important step toward a comprehensive analysis of how these particular motifs mediate, via electrostatic interactions, various molecular processes such as protein sorting, translocation, docking, orientation and binding to DNA and to other proteins. Few algorithms that specifically identify these charge clusters have been designed and described in the literature. In this study, 197 distinctive human viral proteomes were screened for the occurrence of charge clusters (CC) using a new computational approach.ResultsThree hundred and seventy three CC have been identified within the 2549 viral protein sequences screened. The number of protein sequences that are CC-free is 2176 (85.3 %) while 150 and 180 proteins contained positive charge (PCC) and negative charge clusters (NCC), respectively. The NCCs (211 detected) were more prevalent than PCC (162). PCC-containing proteins are significantly longer than those having NCCs (p = 2.10-16). The most prevalent virus families having PCC and NCC were Herpesviridae followed by Papillomaviridae. However, the single-strand RNA group has in average three times more NCC than PCC. According to the functional domain classification, a significant difference in distribution was observed between PCC and NCC (p = 2. 10−8) with the occurrence of NCCs being more frequent in C-terminal region while PCC more often fall within functional domains. Only 29 proteins sequences contained both NCC and PCC. Moreover, 101 NCC were conserved in 84 proteins while only 62 PCC were conserved in 60 protein sequences. To understand the mechanism by which the membrane translocation functionalities are embedded in viral proteins, we screened our PCC for sequences corresponding to cell-penetrating peptides (CPPs) using two online databases: CellPPd and CPPpred. We found that all our PCCs, having length varying from 7 to 30 amino-acids were predicted as CPPs. Experimental validation is required to improve our understanding of the role of these PCCs in viral infection process.ConclusionsScreening distinctive cluster charges in viral proteomes suggested a functional role of these protein regions and might provide potential clues to improve the current understanding of viral diseases in order to tailor better preventive and therapeutic approaches.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3086-3) contains supplementary material, which is available to authorized users.
Highlights
The identification of charge clusters in proteins and their mapping within the protein structure sequence is an important step toward a comprehensive analysis of how these particular motifs mediate, via electrostatic interactions, various molecular processes such as protein sorting, translocation, docking, orientation and binding to Deoxyribonucleic acid (DNA) and to other proteins
Screening distinctive cluster charges in viral proteomes suggested a functional role of these protein regions and might provide potential clues to improve the current understanding of viral diseases in order to tailor better preventive and therapeutic approaches
Description of studied proteomes In this study, the biggest proteome was that of the Human cytomegalovirus which contained 191 proteins and the smallest one contained just a single protein and this was the case of 23 viruses (1 Eechovirus, 9 Hepatitis, 3 Parechovirus, 3 Enterovirus, 7 Rhinovirus)
Summary
The identification of charge clusters (runs of charged residues) in proteins and their mapping within the protein structure sequence is an important step toward a comprehensive analysis of how these particular motifs mediate, via electrostatic interactions, various molecular processes such as protein sorting, translocation, docking, orientation and binding to DNA and to other proteins. These clusters of charged residues are often grouped, producing local concentrations of charge within CB, called charge clusters These regions are most of the time present at the surface of the tertiary or quaternary structure of proteins and contribute to their stability, folding and/or activation as have been supposedly suggested for some proteins families [16]. They have been described for the first time in association with functional domains of cellular transcription factors by Brendel and Karlin [17]. The presence of both positive and negative charge clusters in the same protein sequence, named mixed charge clusters, is thought to contribute in stabilizing and facilitating quaternary structure formation [23]
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