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

Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

9.8K
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....
9.8K
Covalently Linked Protein Regulators02:04

Covalently Linked Protein Regulators

2.1K
2.1K
Protein Complexes with Interchangeable Parts01:57

Protein Complexes with Interchangeable Parts

3.0K
Groups of proteins may form a complex where each protein in this complex has a different role in the overall execution of the complex’s function. Often some of the proteins in the complex can be replaced by a closely related variant to give a complex that contains many of the same components yet is functionally distinct.
The SCF ubiquitin ligase is a protein complex of five individual proteins. This complex attaches ubiquitin to other target proteins to mark them for degradation. In order...
3.0K
Conserved Binding Sites01:49

Conserved Binding Sites

5.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.2K
Structural Protein Function01:56

Structural Protein Function

3.3K
3.3K
Structural Protein Function01:56

Structural Protein Function

30.2K
Structural proteins are a category of proteins responsible for functions ranging from cell shape and movement to providing support to major structures such as bones, cartilage, hair, and muscles. This group includes proteins such as collagen, actin, myosin, and keratin.
Collagen, the most abundant protein in mammals, is found throughout the body. In connective tissue, such as skin, ligaments, and tendons, it provides tensile strength and elasticity.  In bones and teeth, it mineralizes to...
30.2K

You might also read

Related Articles

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

Sort by
Same author

Molecular Origin of <sup>31</sup>P NMR Chemical Shifts of Phosphate Groups with Bivalent Counterions.

The journal of physical chemistry. B·2026
Same author

HBV HBx protein masks epigenetic reader Spindlin1 via an inter-molecular zinc finger to subvert transcriptional control.

Nature communications·2026
Same author

Correction: Dynamic conformational equilibria in the active states of KRAS and NRAS.

RSC chemical biology·2026
Same author

A <sup>13</sup>C<sup>β</sup> CEST experiment with improved sensitivity for the characterization of protein excited states.

Journal of magnetic resonance (San Diego, Calif. : 1997)·2026
Same author

The vacuolar tauopathy-associated mutation D395G confers redox sensitivity to p97/VCP.

bioRxiv : the preprint server for biology·2026
Same author

The dynamic and heterogeneous structure of the non-canonical inflammasome.

bioRxiv : the preprint server for biology·2026
Same journal

Chemotactic self-organization captures the dynamics of mammalian hair follicle patterning.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Tomographic imaging of superconducting order using particle-hole interference.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Inhibitory potential of autologous neutralizing antibodies sets quantitative limits on the rebound-competent HIV-1 reservoir.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Inferring epidemiological parameters under an infectious phylogeography model with visitor dynamics.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Analytical modeling for suction cup designs for skin-interfaced wearable devices.

Proceedings of the National Academy of Sciences of the United States of America·2026
Same journal

Improving cell-free metabolism through direct integration of artificial respiratory chains.

Proceedings of the National Academy of Sciences of the United States of America·2026
See all related articles

Related Experiment Video

Updated: Feb 25, 2026

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

3.0K

Exploiting conformational plasticity in the AAA+ protein VCP/p97 to modify function.

Anne Kathrin Schütz1,2,3, Enrico Rennella1,2,3, Lewis E Kay4,2,3,5

  • 1Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.

Proceedings of the National Academy of Sciences of the United States of America
|August 2, 2017
PubMed
Summary
This summary is machine-generated.

Researchers identified key sites in the p97/VCP protein that can restore normal function in degenerative disease mutants. Targeting these hotspots may lead to new therapies for bone, muscle, and neurological disorders.

Keywords:
IBMPFD disease mutantsconformational plasticitydomain equilibriummethyl-TROSY NMRp97/VCP

More Related Videos

Purification of Hsp104, a Protein Disaggregase
07:17

Purification of Hsp104, a Protein Disaggregase

Published on: September 30, 2011

17.8K
Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking
11:33

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking

Published on: December 17, 2013

6.6K

Related Experiment Videos

Last Updated: Feb 25, 2026

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
05:52

Reconstitution of Msp1 Extraction Activity with Fully Purified Components

Published on: August 10, 2021

3.0K
Purification of Hsp104, a Protein Disaggregase
07:17

Purification of Hsp104, a Protein Disaggregase

Published on: September 30, 2011

17.8K
Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking
11:33

Monitoring the Assembly of a Secreted Bacterial Virulence Factor Using Site-specific Crosslinking

Published on: December 17, 2013

6.6K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • p97/VCP, an AAA+ ATPase, is linked to degenerative diseases affecting bone, muscle, and the central nervous system.
  • Disease-causing mutations in p97/VCP disrupt its N-terminal domain (NTD) dynamics, affecting adaptor binding and protein function.
  • Understanding the conformational dynamics of p97/VCP is crucial for developing therapeutic strategies.

Purpose of the Study:

  • To explore the conformational plasticity of the p97/VCP system.
  • To identify specific "hotspots" that can restore wild-type function in disease mutants.
  • To investigate therapeutic strategies for p97/VCP-related degenerative diseases.

Main Methods:

  • Utilized extensive mutagenesis, focusing on conservative substitutions of hydrophobic residues.
  • Employed Methyl-TROSY-based NMR studies to analyze conformational dynamics.
  • Investigated the binding of the UBXD1 adaptor protein to wild-type and mutant p97/VCP.

Main Results:

  • Identified key mutation sites that alter the NTD equilibrium, primarily at the NTD-D1 domain interface.
  • Demonstrated that a secondary mutation can restore the wild-type NTD position and UBXD1 binding in a severe R155C disease mutant.
  • Showcased the potential for restoring p97/VCP function by targeting specific sites.

Conclusions:

  • The conformational plasticity of p97/VCP offers opportunities for therapeutic intervention.
  • Targeting identified hotspots can restore normal NTD dynamics and adaptor binding in disease mutants.
  • This research provides a foundation for developing drugs to treat p97/VCP-associated degenerative diseases.