Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Export of Misfolded Proteins out of the ER01:32

Export of Misfolded Proteins out of the ER

3.3K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.3K
Regulation of the Unfolded Protein Response01:31

Regulation of the Unfolded Protein Response

2.3K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.3K
The Unfolded Protein Response01:37

The Unfolded Protein Response

4.3K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
4.3K
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

2.3K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
2.3K
Protein Modifications in the RER01:26

Protein Modifications in the RER

4.9K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
4.9K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

6.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
6.7K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

<i>Siphoviridae</i> phage tails co-enrich with ex vivo amyloids.

bioRxiv : the preprint server for biology·2026
Same author

Helical reconstruction of amyloids in cryoSPARC.

Acta crystallographica. Section F, Structural biology communications·2026
Same author

Impaired lipoprotein secretion by APOE4 leads to lysosomal and mitochondrial dysfunction in human microglia.

bioRxiv : the preprint server for biology·2026
Same author

Three-Dimensional Visualization and Proteomic Analysis of Human Cardiac Transthyretin Amyloidosis Tissue Reveals Microangiopathy and Capillary Occlusion.

Journal of the American Heart Association·2026
Same author

DM: a simple solution to suppress air-water interface interactions in cryo-EM.

bioRxiv : the preprint server for biology·2026
Same author

Survey of the human proteostasis network: the ubiquitin-proteasome system.

bioRxiv : the preprint server for biology·2026
Same journal

Genetic Impacts on Variability of Body Fat Distribution Uncover Gene-Environment and Gene-Gene Interactions.

bioRxiv : the preprint server for biology·2026
Same journal

16S ribosomal RNA modification drives transcript-specific translation efficiency.

bioRxiv : the preprint server for biology·2026
Same journal

FlcE latches onto the FliL-stator complex to turbocharge flagellar motility in <i>Borrelia burgdorferi</i>.

bioRxiv : the preprint server for biology·2026
Same journal

Synaptic pruning, myelination and the emergence of psychiatric disorders in late adolescence.

bioRxiv : the preprint server for biology·2026
Same journal

Structural and functional insights into the Rcs phosphorelay.

bioRxiv : the preprint server for biology·2026
Same journal

The structural basis of RanGAP1 regulation and catalysis in nuclear transport.

bioRxiv : the preprint server for biology·2026
See all related articles

Related Experiment Video

Updated: May 13, 2025

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
11:09

Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

Published on: August 1, 2018

10.6K

Phenylhydrazone-based Endoplasmic Reticulum Proteostasis Regulator Compounds with Enhanced Biological Activity.

Gabriel M Kline, Lisa Boinon, Adrian Guerrero

    Biorxiv : the Preprint Server for Biology
    |April 16, 2025
    PubMed
    Summary
    This summary is machine-generated.

    Researchers identified a new drug class that improves endoplasmic reticulum (ER) proteostasis by targeting protein disulfide isomerases. These compounds activate the ATF6 pathway, correcting protein misfolding in diseases like A1AT deficiency and epilepsy.

    More Related Videos

    High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
    05:33

    High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

    Published on: November 9, 2020

    9.3K
    Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
    10:44

    Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

    Published on: May 15, 2019

    13.1K

    Related Experiment Videos

    Last Updated: May 13, 2025

    Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation
    11:09

    Constructing Thioether/Vinyl Sulfide-tethered Helical Peptides Via Photo-induced Thiol-ene/yne Hydrothiolation

    Published on: August 1, 2018

    10.6K
    High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
    05:33

    High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

    Published on: November 9, 2020

    9.3K
    Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
    10:44

    Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

    Published on: May 15, 2019

    13.1K

    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Pharmacology

    Background:

    • Endoplasmic reticulum (ER) proteostasis is crucial for preventing protein misfolding diseases.
    • Existing compounds lack defined mechanisms for enhancing ER proteostasis.
    • The compound AA263 was previously shown to promote ER proteostasis via ATF6 activation.

    Purpose of the Study:

    • To identify the protein target(s) of AA263.
    • To develop improved analogs of AA263 for enhanced ER proteostasis regulation.
    • To demonstrate the therapeutic potential of these analogs in protein misfolding disorders.

    Main Methods:

    • Chemical proteomics to identify AA263 targets.
    • Medicinal chemistry to synthesize next-generation analogs.
    • Cellular assays to assess ATF6 activation and proteostasis correction.

    Main Results:

    • AA263 covalently targets ER protein disulfide isomerases, explaining its ATF6 activation mechanism.
    • Novel AA263 analogs exhibit enhanced potency and efficacy for ATF6 activation.
    • These analogs correct protein misfolding and trafficking defects in α1-antitrypsin and GABAA receptor variants.

    Conclusions:

    • AA263 analogs represent a promising new class of ER proteostasis regulators.
    • Targeting ER protein disulfide isomerases offers a viable strategy for treating protein misfolding diseases.
    • These compounds show potential for correcting imbalanced ER proteostasis in diverse disorders.