Original Research ARTICLE
Charge and polarity preferences for N-glycosylation: a genome-wide in silico study and its implications regarding constitutive proliferation and adhesion of carcinoma cells
- 1Beijing Institute of Genomics, Chinese Academy of Sciences, China
- 2University of Chinese Academy of Sciences (UCAS), China
- 3Institute of Molecular Sciences and Bioinformatics, Pakistan
- 4Department of Physics, Government College University, Pakistan
- 5Department of Computer Science, COMSATS, Institute of Information Technology, Pakistan
- 6Panjwani Centre for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Pakistan
The structural and functional diversity of the human proteome is mediated by N- and O-linked glycosylations that define the individual properties of extracellular and membrane-associated proteins. In this study, we utilized different computational tools to perform in silico based genome-wide mapping of 1117 human proteins and unravel the contribution of both penultimate and vicinal amino acids for the asparagine-based, site-specific N-glycosylation. Our results correlate the non-canonical involvement of charge and polarity environment of classified amino acids (designated as L, O, A, P and N groups) in the N-glycosylation process, as validated by NetNGlyc predictions, and 130 literature-reported human proteins. From our results, particular charge and polarity combinations of non-polar aliphatic, acidic, basic and aromatic polar side chain environment, of both penultimate and vicinal amino acids were found to promote the N-glycosylation process. However, the alteration in side-chain charge and polarity environment of genetic variants, particularly in the vicinity of Asn containing epitope, may induce constitutive glycosylation (e.g. aberrant glycosylation at preferred and non-preferred sites) of membrane proteins causing constitutive proliferation and triggering epithelial-to-mesenchymal transition (EMT). The current genome-wide mapping of 1117 proteins (2,909 asparagine residues) was used to explore charge- and polarity-based mechanistic constraints in N-glycosylation, and discuss alterations of the neoplastic phenotype that can be ascribed to N-glycosylation at preferred and non-preferred sites.
Keywords: N-glycosylation, Human proteins, Genome-wide mapping, Charge and polarity, EGFR, Cancer, Cadherins, EMT.
Received: 27 Sep 2017;
Accepted: 29 Jan 2018.
Edited by:Stephan Von Gunten, University of Bern, Switzerland
Reviewed by:Vered Padler-Karavani, Tel Aviv University, Israel
Heinz Laubli, University of Basel, Switzerland
Copyright: © 2018 Hussain, Iqbal, Qazi and Hoessli. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mr. Zeeshan Iqbal, Institute of Molecular Sciences and Bioinformatics, Lahore, Pakistan, email@example.com