Related Experiment Video

Updated: Oct 7, 2025

Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques
08:58

Characterization of Glycoproteins with the Immunoglobulin Fold by X-Ray Crystallography and Biophysical Techniques

Published on: July 5, 2018

12.8K

N-Glycosylation Facilitates 4-1BB Membrane Localization by Avoiding Its Multimerization

Ruoxuan Sun1, Alyssa Min Jung Kim1, Allison A Murray1

  • 1Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907, USA.

Cells
|January 11, 2022
PubMed

Insights

N-glycosylation controls 4-1BB protein abundance by preventing its intracellular accumulation. This ensures proper membrane transport and turnover, crucial for T cell immunity in cancer therapy.

Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • 4-1BB is a T cell costimulatory receptor vital for anti-tumor immunity.
  • Understanding 4-1BB intracellular regulation is key for optimizing cancer therapies.
  • N-glycosylation is a known modification of 4-1BB, but its functional significance is unclear.

Purpose of the Study:

  • To investigate the impact of N-glycosylation on 4-1BB's ligand interaction, stability, and cellular localization.
  • To elucidate the role of N-glycosylation in regulating 4-1BB's intracellular processing and membrane expression.

Main Methods:

  • Biochemical assays
  • Biophysical techniques
  • Cell-biological approaches

Main Results:

  • N-glycosylation prevents 4-1BB oligomerization, facilitating its transport to the cell membrane.
  • Absence of N-glycosylation leads to aberrant intracellular accumulation and reduced membrane insertion of 4-1BB.
  • N-glycosylation regulates 4-1BB protein abundance, controlling its cell surface availability.

Conclusions:

  • N-glycosylation is essential for the proper trafficking and function of 4-1BB.
  • The N-glycosylation-dependent regulation of 4-1BB abundance offers a mechanism to control T cell activation.
  • This study enhances understanding of 4-1BB biology, aiding its therapeutic development for cancer treatment.
Keywords:
4-1BBN-glycosylationdegradationoligomerization

More Related Videos

Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein07:20

Author Spotlight: Imaging ATG9A, a Multi-Spanning Membrane Protein

Published on: June 16, 2023

2.3K
Generation of Null Mutants to Elucidate the Role of Bacterial Glycosyltransferases in Bacterial Motility12:29

Generation of Null Mutants to Elucidate the Role of Bacterial Glycosyltransferases in Bacterial Motility

Published on: March 11, 2022

2.4K

Related Concept Videos

Oligosaccharide Assembly01:24

Oligosaccharide Assembly

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...
3.0K
Protein Glycosylation01:25

Protein Glycosylation

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...
7.6K
GPI Anchoring of Proteins in the ER Membrane01:29

GPI Anchoring of Proteins in the ER Membrane

GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
4.5K
Protein Folding Quality Check in the RER01:29

Protein Folding Quality Check in the RER

ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
4.0K
Lipids as Anchors01:32

Lipids as Anchors

In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
6.3K
Membrane Carbohydrates01:30

Membrane Carbohydrates

The plasma membrane is a dynamic barrier composed of lipids, proteins, and carbohydrates. It is the epicenter of many cellular processes required for cell growth and survival. Carbohydrates have unique structural and chemical properties that help the plasma membrane to carry out its functions effectively.
Membrane carbohydrates do not have any hydrophobic region and are exclusively located on the cell's outer surface. The addition of sugar molecules or glycosylation of proteins happens in...
6.2K