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

Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

6.9K
The translocon complex situated on the ER membrane is the main gateway for the protein secretory pathway. It facilitates the transport of nascent peptides into the ER lumen and their insertion into the ER membrane.
Sec61 protein conducting channel
In eukaryotes, the translocon complex comprises a core heterotrimeric translocator channel called the Sec61 complex. This channel includes three transmembrane proteins, Sec61α, Sec61β, and Sec61γ, and is the largest subunit of the...
6.9K
Insertion of Multi-pass Transmembrane Proteins in the RER01:29

Insertion of Multi-pass Transmembrane Proteins in the RER

18.7K
The rough ER membrane synthesizes, assembles, and embeds transmembrane proteins in diverse topologies. These proteins function as transporters or channels and can remain in the ER membrane or are sent to the Golgi complex, lysosome, and cell membrane.
The multipass transmembrane proteins are the type IV integral membrane proteins with multiple topogenic sequences determining their spatial arrangement in the ER membrane. Nearly all multipass proteins lack a cleavable signal sequence and use...
18.7K
Insertion of Single-pass Transmembrane Proteins in the RER01:26

Insertion of Single-pass Transmembrane Proteins in the RER

18.2K
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...
18.2K
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

5.0K
Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
5.0K
Assembly of the Lipid Bilayer in the ER01:28

Assembly of the Lipid Bilayer in the ER

4.3K
Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
4.3K
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

3.9K
Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.9K

You might also read

Related Articles

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

Sort by
Same author

Structural evolution of the MTCH family of mitochondrial insertases.

Science advances·2026
Same author

Design principles of human membrane protein topology.

The Journal of cell biology·2026
Same author

Structural evolution of the MTCH family of mitochondrial insertases.

bioRxiv : the preprint server for biology·2026
Same author

Global analysis of translocon remodeling during protein synthesis at the ER.

Nature structural & molecular biology·2025
Same author

Architecture of the UBR4 complex, a giant E4 ligase central to eukaryotic protein quality control.

Science (New York, N.Y.)·2025
Same author

Alpha-synuclein interacts with regulators of ATP homeostasis in mitochondria.

Nature communications·2025

Related Experiment Video

Updated: Feb 16, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
06:45

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

Published on: May 26, 2011

15.7K

The ER membrane protein complex is a transmembrane domain insertase.

Alina Guna1, Norbert Volkmar2, John C Christianson2

  • 1Medical Research Council (MRC) Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.

Science (New York, N.Y.)
|December 16, 2017
PubMed
Summary

The ER membrane protein complex (EMC) acts as a transmembrane domain insertase, essential for inserting tail-anchored proteins that bypass known pathways. This discovery clarifies a crucial step in membrane protein biogenesis.

More Related Videos

Co-Translational Insertion of Membrane Proteins into Preformed Nanodiscs
08:24

Co-Translational Insertion of Membrane Proteins into Preformed Nanodiscs

Published on: November 19, 2020

3.9K
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

Related Experiment Videos

Last Updated: Feb 16, 2026

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
06:45

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

Published on: May 26, 2011

15.7K
Co-Translational Insertion of Membrane Proteins into Preformed Nanodiscs
08:24

Co-Translational Insertion of Membrane Proteins into Preformed Nanodiscs

Published on: November 19, 2020

3.9K
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

Area of Science:

  • Cell Biology
  • Biochemistry
  • Molecular Biology

Background:

  • Protein insertion into cellular membranes is vital but complex.
  • Existing pathways inadequately explain the insertion of all membrane proteins, particularly tail-anchored ones.
  • The function of the ER membrane protein complex (EMC) in protein insertion is not fully understood.

Purpose of the Study:

  • To investigate the mechanism of insertion for tail-anchored membrane proteins.
  • To identify the cellular machinery responsible for inserting proteins that bypass known pathways.
  • To elucidate the role of the ER membrane protein complex (EMC) in transmembrane domain insertion.

Main Methods:

  • Utilized biochemical assays to test protein insertion pathways.
  • Investigated the role of calmodulin and the ER membrane protein complex (EMC) in vitro and in cellular systems.
  • Reconstituted EMC function using purified protein in synthetic liposomes.

Main Results:

  • Known membrane insertion pathways are ineffective for moderately hydrophobic tail-anchored proteins.
  • Calmodulin shields these proteins in the cytosol before ER interaction.
  • The ER membrane protein complex (EMC) is essential for efficient insertion of these proteins.
  • Purified EMC catalyzes transmembrane domain insertion in a reconstituted system.

Conclusions:

  • The ER membrane protein complex (EMC) functions as a specific transmembrane domain insertase.
  • This insertase activity explains the pleiotropic phenotypes associated with EMC.
  • Identified a novel pathway for tail-anchored membrane protein biogenesis.