scholarly journals Direct comparison of derivatization strategies for LC-MS/MS analysis of N-glycans

The Analyst ◽  
2017 ◽  
Vol 142 (23) ◽  
pp. 4446-4455 ◽  
Author(s):  
Shiyue Zhou ◽  
Lucas Veillon ◽  
Xue Dong ◽  
Yifan Huang ◽  
Yehia Mechref
Keyword(s):  
Protein Folding ◽  
Protein Glycosylation ◽  
Post Translational Modification ◽  
P Protein ◽  
Ms Analysis ◽  
And Function

Protein glycosylation is a common post-translational modification that has significant impacts on protein folding, lifespan, conformation, distribution and function.

scholarly journals The impact of O-glycan chemistry on the stability of intrinsically disordered proteins

2018 ◽  
Vol 9 (15) ◽  
pp. 3710-3715 ◽  
Author(s):  
Erica T. Prates ◽  
Xiaoyang Guan ◽  
Yaohao Li ◽  
Xinfeng Wang ◽  
Patrick K. Chaffey ◽  
...  
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Protein Glycosylation ◽  
Disordered Proteins ◽  
Biological Functions ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
P Protein ◽  
The Stability ◽  
The Impact

Protein glycosylation is a diverse post-translational modification that serves myriad biological functions.

Impact of protein glycosylation on lipoprotein metabolism and atherosclerosis

2020 ◽  
Author(s):  
Angela Pirillo ◽  
Monika Svecla ◽  
Alberico Luigi Catapano ◽  
Adriaan G Holleboom ◽  
Giuseppe Danilo Norata
Keyword(s):  
Genetic Diseases ◽  
Clinical Manifestations ◽  
Lipoprotein Metabolism ◽  
Protein Glycosylation ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Lipoprotein Receptors ◽  
Additional Information ◽  
Rare Genetic Diseases ◽  
And Function

Abstract Protein glycosylation is a post-translational modification consisting in the enzymatic attachment of carbohydrate chains to specific residues of the protein sequence. Several types of glycosylation have been described, with N-glycosylation and O-glycosylation being the most common types impacting on crucial biological processes, such as protein synthesis, trafficking, localization, and function. Genetic defects in genes involved in protein glycosylation may result in altered production and activity of several proteins, with a broad range of clinical manifestations, including dyslipidaemia and atherosclerosis. A large number of apolipoproteins, lipoprotein receptors, and other proteins involved in lipoprotein metabolism are glycosylated, and alterations in their glycosylation profile are associated with changes in their expression and/or function. Rare genetic diseases and population genetics have provided additional information linking protein glycosylation to the regulation of lipoprotein metabolism.

scholarly journals N-Glycosylation as a Tool to Study Antithrombin Secretion, Conformation, and Function

2021 ◽  
Vol 22 (2) ◽  
pp. 516
Author(s):  
Sonia Águila ◽  
Rosina Noto ◽  
Ginés Luengo-Gil ◽  
Salvador Espín ◽  
Nataliya Bohdan ◽  
...  
Keyword(s):  
Protein Folding ◽  
Pivotal Role ◽  
Type I ◽  
Post Translational Modification ◽  
Thrombotic Risk ◽  
Functional Variants ◽  
Glycosylation Sites ◽  
Natural Variants ◽  
And Function

N-linked glycosylation is a crucial post-translational modification involved in protein folding, function, and clearance. N-linked glycosylation is also used therapeutically to enhance the half-lives of many proteins. Antithrombin, a serpin with four potential N-glycosylation sites, plays a pivotal role in hemostasis, wherein its deficiency significantly increases thrombotic risk. In this study, we used the introduction of N-glycosylation sites as a tool to explore what effect this glycosylation has on the protein folding, secretion, and function of this key anticoagulant. To accomplish this task, we introduced an additional N-glycosylation sequence in each strand. Interestingly, all regions that likely fold rapidly or were surrounded by lysines were not glycosylated even though an N-glycosylation sequon was present. The new sequon in the strands of the A- and B-sheets reduced secretion, and the B-sheet was more sensitive to these changes. However, the mutations in the strands of the C-sheet allowed correct folding and secretion, which resulted in functional variants. Therefore, our study revealed crucial regions for antithrombin secretion and could potentially apply to all serpins. These results could also help us understand the functional effects of natural variants causing type-I deficiencies.

Protein glycosylation in Leishmania spp.

2020 ◽  
Vol 16 (5) ◽  
pp. 407-424
Author(s):  
Simon Ngao Mule ◽  
Joyce Silva Saad ◽  
Livia Rosa Fernandes ◽  
Beatriz S. Stolf ◽  
Mauro Cortez ◽  
...  
Keyword(s):  
Protein Glycosylation ◽  
Vertebrate Host ◽  
Post Translational Modification ◽  
Host Interaction ◽  
P Protein ◽  
Leishmania Spp

Protein glycosylation is a co- and post-translational modification that, in Leishmania parasites, plays key roles in vector–parasite–vertebrate host interaction.

O-glycan recognition and function in mice and human cancers

2020 ◽  
Vol 477 (8) ◽  
pp. 1541-1564 ◽  
Author(s):  
Gabrielle E. Cervoni ◽  
Jane J. Cheng ◽  
Kathryn A. Stackhouse ◽  
Jamie Heimburg-Molinaro ◽  
Richard D. Cummings
Keyword(s):  
Tumor Cells ◽  
Tumor Development ◽  
Cell Types ◽  
Protein Glycosylation ◽  
Ca 125 ◽  
Post Translational Modification ◽  
Tn Antigen ◽  
Altered Expression ◽  
Sialyl Tn Antigen ◽  
And Function

Protein glycosylation represents a nearly ubiquitous post-translational modification, and altered glycosylation can result in clinically significant pathological consequences. Here we focus on O-glycosylation in tumor cells of mice and humans. O-glycans are those linked to serine and threonine (Ser/Thr) residues via N-acetylgalactosamine (GalNAc), which are oligosaccharides that occur widely in glycoproteins, such as those expressed on the surfaces and in secretions of all cell types. The structure and expression of O-glycans are dependent on the cell type and disease state of the cells. There is a great interest in O-glycosylation of tumor cells, as they typically express many altered types of O-glycans compared with untransformed cells. Such altered expression of glycans, quantitatively and/or qualitatively on different glycoproteins, is used as circulating tumor biomarkers, such as CA19-9 and CA-125. Other tumor-associated carbohydrate antigens (TACAs), such as the Tn antigen and sialyl-Tn antigen (STn), are truncated O-glycans commonly expressed by carcinomas on multiple glycoproteins; they contribute to tumor development and serve as potential biomarkers for tumor presence and stage, both in immunohistochemistry and in serum diagnostics. Here we discuss O-glycosylation in murine and human cells with a focus on colorectal, breast, and pancreatic cancers, centering on the structure, function and recognition of O-glycans. There are enormous opportunities to exploit our knowledge of O-glycosylation in tumor cells to develop new diagnostics and therapeutics.

scholarly journals Sumoylation regulates the assembly and activity of the SMN complex

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Giulietta M. Riboldi ◽  
Irene Faravelli ◽  
Takaaki Kuwajima ◽  
Nicolas Delestrée ◽  
Georgia Dermentzaki ◽  
...  
Keyword(s):  
Survival Rate ◽  
Muscular Atrophy ◽  
Motor Deficits ◽  
Cellular Distribution ◽  
Post Translational Modification ◽  
Smn Complex ◽  
Sensory Motor ◽  
Motor Neuron Loss ◽  
And Function ◽  
Small Nuclear Ribonucleoproteins

AbstractSMN is a ubiquitously expressed protein and is essential for life. SMN deficiency causes the neurodegenerative disease spinal muscular atrophy (SMA), the leading genetic cause of infant mortality. SMN interacts with itself and other proteins to form a complex that functions in the assembly of ribonucleoproteins. SMN is modified by SUMO (Small Ubiquitin-like Modifier), but whether sumoylation is required for the functions of SMN that are relevant to SMA pathogenesis is not known. Here, we show that inactivation of a SUMO-interacting motif (SIM) alters SMN sub-cellular distribution, the integrity of its complex, and its function in small nuclear ribonucleoproteins biogenesis. Expression of a SIM-inactivated mutant of SMN in a mouse model of SMA slightly extends survival rate with limited and transient correction of motor deficits. Remarkably, although SIM-inactivated SMN attenuates motor neuron loss and improves neuromuscular junction synapses, it fails to prevent the loss of sensory-motor synapses. These findings suggest that sumoylation is important for proper assembly and function of the SMN complex and that loss of this post-translational modification impairs the ability of SMN to correct selective deficits in the sensory-motor circuit of SMA mice.

Robustness and generalization of structure-based models for protein folding and function

2009 ◽  
Vol 77 (4) ◽  
pp. 881-891 ◽  
Author(s):  
Heiko Lammert ◽  
Alexander Schug ◽  
José N. Onuchic
Keyword(s):  
Protein Folding ◽  
And Function

scholarly journals Intrinsic disorder in protein domains contributes to both organism complexity and clade-specific functions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chao Gao ◽  
Chong Ma ◽  
Huqiang Wang ◽  
Haolin Zhong ◽  
Jiayin Zang ◽  
...  
Keyword(s):  
Biological Significance ◽  
Protein Domains ◽  
Functional Requirements ◽  
Post Translational Modification ◽  
Intrinsically Disordered ◽  
Genome Wide ◽  
Complex Functions ◽  
Disorder Degree ◽  
Functional Features ◽  
And Function

AbstractInterestingly, some protein domains are intrinsically disordered (abbreviated as IDD), and the disorder degree of same domains may differ in different contexts. However, the evolutionary causes and biological significance of these phenomena are unclear. Here, we address these issues by genome-wide analyses of the evolutionary and functional features of IDDs in 1,870 species across the three superkingdoms. As the result, there is a significant positive correlation between the proportion of IDDs and organism complexity with some interesting exceptions. These phenomena may be due to the high disorder of clade-specific domains and the different disorder degrees of the domains shared in different clades. The functions of IDDs are clade-specific and the higher proportion of post-translational modification sites may contribute to their complex functions. Compared with metazoans, fungi have more IDDs with a consecutive disorder region but a low disorder ratio, which reflects their different functional requirements. As for disorder variation, it’s greater for domains among different proteins than those within the same proteins. Some clade-specific ‘no-variation’ or ‘high-variation’ domains are involved in clade-specific functions. In sum, intrinsic domain disorder is related to both the organism complexity and clade-specific functions. These results deepen the understanding of the evolution and function of IDDs.

scholarly journals Glial Hedgehog and lipid metabolism regulate neural stem cell proliferation in Drosophila

2020 ◽  
Author(s):  
Qian Dong ◽  
Michael Zavortink ◽  
Francesca Froldi ◽  
Sofya Golenkina ◽  
Tammy Lam ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cell Cycle Progression ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Post Translational Modification ◽  
Final Size ◽  
Neural Lineage ◽  
Signalling Molecule ◽  
Lipid Metabolism Genes ◽  
And Function

AbstractThe final size and function of the adult central nervous system (CNS) is determined by neuronal lineages generated by neural stem cells (NSCs) in the developing brain. In Drosophila, NSCs called neuroblasts (NBs) reside within a specialised microenvironment called the glial niche. Here, we explore non-autonomous glial regulation of NB proliferation. We show that lipid droplets (LDs) which reside within the glial niche are closely associated with the signalling molecule Hedgehog (Hh). Under physiological conditions, cortex glial Hh is autonomously required to sustain niche chamber formation, and non-autonomously restrained to prevent ectopic Hh signalling in the NBs. In the context of cortex glial overgrowth, induced by Fibroblast Growth Factor (FGF) activation, Hh and lipid storage regulators Lsd-2 and Fasn1 were upregulated, resulting in activation of Hh signalling in the NBs; which in turn disrupted NB cell cycle progression and reduced neuronal production. We show that the LD regulator Lsd-2 modulates Hh’s ability to signal to NBs, and de novo lipogenesis gene Fasn1 regulates Hh post-translational modification via palmitoylation. Together, our data suggest that the glial niche non-autonomously regulates NB proliferation and neural lineage size via Hh signaling that is modulated by lipid metabolism genes.

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