International Journal of Molecular Sciences

Journal Browser

► Journal Browser

Special Issue Information

Dear Colleagues,

Glycosylation is a biological process that attaches carbohydrates to proteins and lipids. Glycoconjugates have been considered to play important roles in the maintenance of the homeostasis of organisms and in the pathogenesis of various diseases. For instance, glycosphingolipids consist of carbohydrate chains and ceramide and regulate bone metabolism and endocrine metabolism. On the other hand, they are involved in nerve degeneration and the promotion of the malignant properties of cancer cells. As one of the mechanisms, the localization of glycosphingolipids in lipid raft regulates the interaction of membrane molecules to control cellular signaling. As for glycoproteins, it has been known that the fucosylation of N-glycans and O-glycans on various receptors leads to the regulation of signaling in cancer cells.

This Special Issue, entitled Glycoconjugates Function and Metabolism, will cover research topics and current review articles in the field.

Prof. Dr. Kazunori Hamamura
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

glycosylation
glycoconjugates
glycolipids
gangliosides
glycoproteins

Published Papers (2 papers)

Download All Papers

Research

13 pages, 1892 KiB

Open AccessArticle

Integrating Embeddings from Multiple Protein Language Models to Improve Protein O-GlcNAc Site Prediction

by Suresh Pokharel, Pawel Pratyush, Hamid D. Ismail, Junfeng Ma and Dukka B. KC

Int. J. Mol. Sci. 2023, 24(21), 16000; https://doi.org/10.3390/ijms242116000 - 06 Nov 2023

Cited by 1 | Viewed by 2006

Abstract

O-linked β-N-acetylglucosamine (O-GlcNAc) is a distinct monosaccharide modification of serine (S) or threonine (T) residues of nucleocytoplasmic and mitochondrial proteins. O-GlcNAc modification (i.e., O-GlcNAcylation) is involved in the regulation of diverse cellular processes, including transcription, epigenetic modifications, and cell signaling. Despite the great progress in experimentally mapping O-GlcNAc sites, there is an unmet need to develop robust prediction tools that can effectively locate the presence of O-GlcNAc sites in protein sequences of interest. In this work, we performed a comprehensive evaluation of a framework for prediction of protein O-GlcNAc sites using embeddings from pre-trained protein language models. In particular, we compared the performance of three protein sequence-based large protein language models (pLMs), Ankh, ESM-2, and ProtT5, for prediction of O-GlcNAc sites and also evaluated various ensemble strategies to integrate embeddings from these protein language models. Upon investigation, the decision-level fusion approach that integrates the decisions of the three embedding models, which we call LM-OGlcNAc-Site, outperformed the models trained on these individual language models as well as other fusion approaches and other existing predictors in almost all of the parameters evaluated. The precise prediction of O-GlcNAc sites will facilitate the probing of O-GlcNAc site-specific functions of proteins in physiology and diseases. Moreover, these findings also indicate the effectiveness of combined uses of multiple protein language models in post-translational modification prediction and open exciting avenues for further research and exploration in other protein downstream tasks. LM-OGlcNAc-Site’s web server and source code are publicly available to the community. Full article

(This article belongs to the Special Issue Glycoconjugates Function and Metabolism)

► Show Figures

Figure 1

13 pages, 571 KiB

Open AccessArticle

Apolipoprotein-CIII O-Glycosylation, a Link between GALNT2 and Plasma Lipids

by Annemieke Naber, Daniel Demus, Roderick Slieker, Simone Nicolardi, Joline W. J. Beulens, Petra J. M. Elders, Aloysius G. Lieverse, Eric J. G. Sijbrands, Leen M. ’t Hart, Manfred Wuhrer and Mandy van Hoek

Int. J. Mol. Sci. 2023, 24(19), 14844; https://doi.org/10.3390/ijms241914844 - 02 Oct 2023

Cited by 1 | Viewed by 1003

Abstract

Apolipoprotein-CIII (apo-CIII) is involved in triglyceride-rich lipoprotein metabolism and linked to beta-cell damage, insulin resistance, and cardiovascular disease. Apo-CIII exists in four main proteoforms: non-glycosylated (apo-CIII_0a), and glycosylated apo-CIII with zero, one, or two sialic acids (apo-CIII_0c, apo-CIII₁ and apo-CIII₂). Our objective is to determine how apo-CIII glycosylation affects lipid traits and type 2 diabetes prevalence, and to investigate the genetic basis of these relations with a genome-wide association study (GWAS) on apo-CIII glycosylation. We conducted GWAS on the four apo-CIII proteoforms in the DiaGene study in people with and without type 2 diabetes (n = 2318). We investigated the relations of the identified genetic loci and apo-CIII glycosylation with lipids and type 2 diabetes. The associations of the genetic variants with lipids were replicated in the Diabetes Care System (n = 5409). Rs4846913-A, in the GALNT2-gene, was associated with decreased apo-CIII_0a. This variant was associated with increased high-density lipoprotein cholesterol and decreased triglycerides, while high apo-CIII_0a was associated with raised high-density lipoprotein-cholesterol and triglycerides. Rs67086575-G, located in the IFT172-gene, was associated with decreased apo-CIII₂ and with hypertriglyceridemia. In line, apo-CIII₂ was associated with low triglycerides. On a genome-wide scale, we confirmed that the GALNT2-gene plays a major role i O-glycosylation of apolipoprotein-CIII, with subsequent associations with lipid parameters. We newly identified the IFT172/NRBP1 region, in the literature previously associated with hypertriglyceridemia, as involved in apolipoprotein-CIII sialylation and hypertriglyceridemia. These results link genomics, glycosylation, and lipid metabolism, and represent a key step towards unravelling the importance of O-glycosylation in health and disease. Full article

(This article belongs to the Special Issue Glycoconjugates Function and Metabolism)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Glycoconjugates Function and Metabolism

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (2 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI