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

Noncovalent Attractions in Biomolecules02:35

Noncovalent Attractions in Biomolecules

Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
Noncovalent Attractions in Biomolecules02:35

Noncovalent Attractions in Biomolecules

Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
Protein Complex Assembly02:41

Protein Complex Assembly

Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types.  Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Protein Folding01:22

Protein Folding

Overview
Protein Folding01:25

Protein Folding

Proteins are chains of amino acids linked together by peptide bonds. Upon synthesis, a protein folds into a three-dimensional conformation, critical to its biological function. Interactions between its constituent amino acids guide protein folding, and hence the protein structure is primarily dependent on its amino acid sequence.
Protein Structure Is Critical to Its Biological Function
Proteins perform a wide range of biological functions such as catalyzing chemical reactions, providing...
Protein Organization01:13

Protein Organization

Overview

You might also read

Related Articles

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

Sort by
Same author

Lipid composition and mechanical force underlie multi-modal regulation of Piezo1 gating.

Science advances·2026
Same author

The configurational length scale in the self-assembly and modulation of higher-order transient protein structures.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

The density of Braun's Lipoprotein determines vesicle production in E. coli.

PloS one·2025
Same author

Molecular contacts in self-assembling clusters of membrane proteins.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

Electric field-induced pore constriction in the human K<sub>v</sub>2.1 channel.

Proceedings of the National Academy of Sciences of the United States of America·2025
Same author

Higher-order transient membrane protein structures.

Proceedings of the National Academy of Sciences of the United States of America·2024

Related Experiment Video

Updated: Jul 4, 2026

Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides
07:26

Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides

Published on: November 21, 2013

Biomolecular assemblies through weak noncovalent interactions: Higher-order transient structures and their condensate

Roderick MacKinnon1, Christoph A Haselwandter2,3

  • 1Laboratory of Molecular Neurobiology and Biophysics, HHMI, The Rockefeller University, New York, NY 10065.

Proceedings of the National Academy of Sciences of the United States of America
|July 2, 2026
PubMed
Summary

Membrane proteins form transient structures called higher-order transient structures (HOTS) through specific noncovalent interactions. These HOTS act as signaling hubs, with potential roles across cellular compartments.

Keywords:
HOTSbiomolecular condensateshigher-order transient structuresmembrane signalingmolecular crowding

More Related Videos

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates
06:48

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates

Published on: January 5, 2024

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
09:34

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Published on: February 6, 2020

Related Experiment Videos

Last Updated: Jul 4, 2026

Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides
07:26

Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides

Published on: November 21, 2013

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates
06:48

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates

Published on: January 5, 2024

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
09:34

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly

Published on: February 6, 2020

Area of Science:

  • Biophysics
  • Cell Biology
  • Molecular Biology

Background:

  • Membrane proteins can self-organize into spatial patterns via weak noncovalent interactions.
  • These interactions are protein type-specific, leading to the formation of higher-order transient structures (HOTS).
  • HOTS function as transient signaling hubs (10-100 nm) within cell membranes.

Purpose of the Study:

  • To describe conditions necessary for HOTS assembly.
  • To explore the thermodynamic relationship between HOTS and biomolecular condensates.
  • To investigate potential biological roles of HOTS based on their physical properties.

Main Methods:

  • Analysis of spontaneous spatial organization of membrane proteins.
  • Thermodynamic modeling of higher-order transient structures (HOTS) formation.
  • Investigation of protein type-specific interactions driving HOTS assembly.

Main Results:

  • Identified conditions required for the assembly of higher-order transient structures (HOTS).
  • Established the thermodynamic link between HOTS formation and biomolecular condensate principles.
  • Highlighted unique physical properties of HOTS suggesting diverse biological functions.

Conclusions:

  • HOTS represent a significant organizational principle for membrane proteins.
  • The physical properties of HOTS suggest crucial roles in cellular signaling.
  • Further research is needed to understand HOTS in 3D cellular compartments beyond membranes.