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Proteoglycans01:05

Proteoglycans

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Glycans, a class of complex heterogeneous molecules, can be covalently attached to proteins to form glycosylated proteins that regulate various physiological and pathological processes. Glycosylated proteins or glycoproteins comprise N-linked and O-linked oligosaccharides. O-glycosylation is the most common type of protein glycosylation. Here, glycans attach to the oxygen atom of the hydroxyl groups of Serine or Threonine residues. O-linked glycosylation occurs later in protein processing,...
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Protein Glycosylation01:25

Protein Glycosylation

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Glycosylation, the most common post-translational modification for proteins, serves diverse functions. Adding sugars to proteins makes the proteins more resistant to proteolytic digestion. Glycosylated proteins can act as markers and receptors to promote cell-cell adhesion. Additionally, they have many essential quality control functions in the cell, such as correct protein folding and facilitating transport of misfolded proteins to the cytosol, which can be degraded.
Glycosylation occurs in...
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Oligosaccharide Assembly01:24

Oligosaccharide Assembly

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Protein glycosylation starts in the ER lumen and continues in the Golgi apparatus. Glycosyltransferases catalyze the addition of sugar molecules or glycosylation of proteins. Usually, these enzymes add sugars to the hydroxyl groups of selected serine or threonine residues to form O-linked glycans or the amino groups of asparagine residues to form N-linked glycans. Different positions on the same polypeptide chain can contain differently linked glycans.
Multiple sugar molecules that may or may...
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Cystic Fibrosis: Pathogenesis01:23

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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
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Carbohydrate Catabolism01:30

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Carbohydrate catabolism is a fundamental process in cellular metabolism that enables energy extraction from glucose through two primary pathways: cellular respiration and fermentation. Both pathways begin with glycolysis, which operates independently of oxygen availability.Glycolysis: A Shared Starting PointGlycolysis is an oxygen-independent process that breaks down glucose into two molecules of pyruvic acid. During this process, a net gain of two ATP molecules and two NADH molecules is...
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Glycosaminoglycans01:23

Glycosaminoglycans

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Glycosaminoglycans (GAGs), also known as mucopolysaccharides, are long and linear polymers comprising of specific repeating disaccharides - the amino sugar that can be N-acetylglucosamine or N-acetylgalactosamine, and a uronic acid that is usually glucuronic acid or iduronic acid.
GAGS are found in the extracellular matrix of vertebrates, invertebrates, and bacteria. Due to their polar nature they attract water, and serve as excellent lubricants or shock absorbers in an animal body.
Hyaluronic...
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Related Experiment Video

Updated: Jan 9, 2026

Preparation of CD4+ T Cells for Analysis of GD3 and GD2 Ganglioside Membrane Expression by Microscopy
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Insights Into the Pathological Glycosylation Associated With COG6-CDG.

Zuzana Pakanová1, Maroš Krchňák1, Marek Nemčovič1

  • 1Department of Glycobiology, Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovakia.

Human Mutation
|December 9, 2025
PubMed
Summary
This summary is machine-generated.

We identified a novel COG6 variant causing complete loss of COG6 protein function in an infant with multisystemic Congenital Disorders of Glycosylation (CDG). This discovery offers insights into COG6-CDG molecular mechanisms and potential diagnostic biomarkers.

Keywords:
COG6-CDGglycomicsglycoprofilemass spectrometry

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Targeting Cysteine Thiols for in Vitro Site-specific Glycosylation of Recombinant Proteins
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Area of Science:

  • Biochemistry
  • Genetics
  • Molecular Biology

Background:

  • Congenital Disorders of Glycosylation (CDG) are rare inherited metabolic diseases.
  • Defects in protein glycosylation lead to multisystemic clinical manifestations.
  • COG6-CDG is a specific subtype characterized by defects in the COG complex.

Purpose of the Study:

  • To investigate a case of COG6-CDG in an infant with multisystemic involvement.
  • To identify the genetic cause and molecular mechanisms underlying the patient's condition.
  • To explore potential glycobiomarkers for COG6-CDG diagnosis.

Main Methods:

  • Mass spectrometry (MALDI, ESI-Orbitrap) for glycan analysis (N- and O-glycans).
  • Next-generation sequencing for mutation analysis of the COG6 gene.
  • Functional studies assessing COG6 subunit expression, cooperating subunits, and retrograde transport.

Main Results:

  • A novel homozygous variant (c.906_907delinsA) in the COG6 gene was identified, leading to a truncated protein and complete loss of function.
  • Combined N- and O-glycosylation defects were detected, consistent with COG6-CDG.
  • Specific underprocessed N-glycans were identified as potential glycobiomarkers.

Conclusions:

  • The study describes a novel COG6 variant causing severe glycosylation abnormalities and complete loss of protein function.
  • Multiomics analysis elucidated the molecular mechanisms of COG6-CDG and the role of the COG6 gene.
  • The findings highlight significant alterations in the patient's glycophenotype due to the identified mutation.