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

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

7.0K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
7.0K
Conservation of Protein Domains Over Different Proteins02:26

Conservation of Protein Domains Over Different Proteins

14.9K
Protein domains are small structurally independent units that are part of a single amino acid chain.  Although these domains are often structurally independent, they may rely on synergistic effects to perform their functions as part of a larger protein. Protein domains may be conserved within the same organism, as well as across different organisms.
A limited set of protein domains often duplicate and recombine during evolution. These domains can be organized in different combinations to...
14.9K
Ribosomal RNA Synthesis02:53

Ribosomal RNA Synthesis

15.1K
Ribosome synthesis is a highly complex and coordinated process involving more than 200 assembly factors. The synthesis and processing of ribosomal components occurs not only in the nucleolus but also in the nucleoplasm and the cytoplasm of eukaryotic cells.
Ribosome biogenesis begins with the synthesis of 5S and 45S pre-rRNAs by distinct RNA polymerases. The primary transcripts are extensively processed and modified before they are bound and folded by ribosomal proteins and assembly factors,...
15.1K
Mechanisms of Membrane Domain Formation00:59

Mechanisms of Membrane Domain Formation

4.3K
Different physical properties of lipids and proteins allow them to localize and form distinct islands or domains in the membrane. Some membrane domains are formed due to protein-protein interactions, whereas others are formed due to the presence of specific lipids such as sphingolipids and sterols—for example, large proteins, such as bacteriorhodopsin, aggregate and create distinct domains.
Another mechanism for membrane domain formation involves membrane proteins interacting with...
4.3K
Protein-protein Interfaces02:04

Protein-protein Interfaces

14.9K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
14.9K
Insertion of Single-pass Transmembrane Proteins in the RER01:26

Insertion of Single-pass Transmembrane Proteins in the RER

18.7K
Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
18.7K

You might also read

Related Articles

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

Sort by
Same author

Nature's Anaerobic Toolkit: Glycyl Radical Enzymes and Their Expanding Functional and Mechanistic Diversity.

Biochemistry·2026
Same author

The Structural Basis of Malodorant Skatole Formation by the Glycyl Radical Enzyme Indoleacetate Decarboxylase.

bioRxiv : the preprint server for biology·2026
Same author

How a protein repurposes vitamin B12 as a light sensor.

Nature·2026
Same author

A highly dynamic mononuclear non-heme iron enzyme for the two-step isonitrile biosynthesis.

Nature communications·2026
Same author

The cobalamin-binding domain of cobalamin-dependent radical S-adenosylmethionine enzymes: Familiarity in unfamiliar places.

Journal of inorganic biochemistry·2026
Same author

PexR is a noncanonical regulator of the peroxide stress response in bacteria.

Nucleic acids research·2025
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: Mar 13, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
07:11

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Published on: September 28, 2022

3.2K

Structural elements of an NRPS cyclization domain and its intermodule docking domain.

Daniel P Dowling1,2, Yan Kung2, Anna K Croft3

  • 1Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139; daniel.dowling@umb.edu cdrennan@mit.edu.

Proceedings of the National Academy of Sciences of the United States of America
|November 3, 2016
PubMed
Summary
This summary is machine-generated.

Researchers visualized the cyclization domain of EpoB, revealing flexible docking domains and channels for substrate delivery in epothilone biosynthesis. This provides insights into modular polyketide synthase-nonribosomal peptide synthetase systems.

Keywords:
crystal structureepothilonemolecular dynamicsnatural product

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.9K
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

8.1K

Related Experiment Videos

Last Updated: Mar 13, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
07:11

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center

Published on: September 28, 2022

3.2K
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.9K
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

8.1K

Area of Science:

  • Biochemistry
  • Structural Biology
  • Natural Product Biosynthesis

Background:

  • Epothilones are anticancer natural products synthesized by hybrid polyketide synthase (PKS)-nonribosomal peptide synthetase (NRPS) enzymes.
  • The cyclization (Cy) domain of EpoB is crucial for assembling thiazole functionality using substrates from carrier proteins.

Purpose of the Study:

  • To determine the structure of the EpoB cyclization domain with its associated docking domain.
  • To elucidate the mechanism of substrate delivery and catalysis in epothilone biosynthesis.

Main Methods:

  • X-ray crystallography to solve the 2.03-Å resolution structure of the EpoB bidomain unit.
  • Molecular dynamics simulations to assess domain flexibility.
  • Mutagenesis and activity assays to identify catalytic residues.

Main Results:

  • The N-terminal docking domain is flexibly linked to the V-shaped Cy domain.
  • Two distinct channels facilitate simultaneous substrate delivery to the Cy active site.
  • Identified catalytic residues N335 and D449, which differ from the conserved motif in homologous NRPS condensation domains.

Conclusions:

  • The modularity and flexibility of PKS-NRPS components are highlighted.
  • The EpoB Cy domain possesses a unique active site distinct from canonical NRPS condensation domains.
  • Structural insights advance understanding of complex natural product biosynthesis pathways.