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Related Concept Videos

Insertion of Single-pass Transmembrane Proteins in the RER01:26

Insertion of Single-pass Transmembrane Proteins in the RER

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...
Protein Translocation Machinery on the ER Membrane01:28

Protein Translocation Machinery on the ER Membrane

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 translocon complex.
Insertion of Multi-pass Transmembrane Proteins in the RER01:29

Insertion of Multi-pass Transmembrane Proteins in the RER

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...
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

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...
Assembly of the Lipid Bilayer in the ER01:28

Assembly of the Lipid Bilayer in the ER

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...
ER Retrieval Pathway01:45

ER Retrieval Pathway

In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...

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Related Experiment Video

Updated: Jul 8, 2026

Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy
10:49

Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy

Published on: March 5, 2017

Cytosolic transmembrane helices enter the ER membrane through EMC6-driven electrostatic interactions.

Hongyan Zheng1, Wenxue Gu1, Tong Zhou1

  • 1School of Basic Medicine, Tsinghua University, Beijing 100084, China.

Journal of Molecular Cell Biology
|July 7, 2026
PubMed
Summary

The endoplasmic reticulum membrane protein complex (EMC) stabilizes epithelial sodium channel (ENaC) biosynthesis by completing transmembrane domain insertion. This involves electrostatic interactions and a semi-insertase mechanism, crucial for multipass protein biogenesis.

Keywords:
EMCEMC8-KOEMC9-KOENaCTM2b hydrophilicity

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Three-dimensional Characterization of Interorganelle Contact Sites in Hepatocytes using Serial Section Electron Microscopy

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Last Updated: Jul 8, 2026

Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy
10:49

Method to Visualize and Analyze Membrane Interacting Proteins by Transmission Electron Microscopy

Published on: March 5, 2017

Transmembrane Domain Oligomerization Propensity determined by ToxR Assay
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Transmembrane Domain Oligomerization Propensity determined by ToxR Assay

Published on: May 26, 2011

Three-dimensional Characterization of Interorganelle Contact Sites in Hepatocytes using Serial Section Electron Microscopy
09:12

Three-dimensional Characterization of Interorganelle Contact Sites in Hepatocytes using Serial Section Electron Microscopy

Published on: June 9, 2022

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Protein Biochemistry

Background:

  • The Endoplasmic Reticulum Membrane Protein Complex (EMC) is known to assist in the insertion and translocation of transmembrane domains (TMDs) and small terminal domains.
  • The biogenesis of multipass membrane proteins, particularly those with challenging hydrophilic TMDs, remains a complex area of study.

Purpose of the Study:

  • To investigate the role of the EMC in the biosynthesis of the epithelial sodium channel (ENaC).
  • To elucidate the mechanism by which EMC facilitates the membrane integration of ENaC's transmembrane domains.
  • To identify other proteins that may utilize similar EMC-mediated insertion mechanisms.

Main Methods:

  • Genetic manipulation to assess the impact of EMC loss on ENaC expression.
  • Biochemical assays to analyze protein-protein interactions between ENaC and EMC components.
  • Bioinformatic analysis to identify potential EMC clients with similar TMD characteristics.

Main Results:

  • EMC is essential for epithelial sodium channel (ENaC) biosynthesis, stabilizing its expression without affecting surface trafficking.
  • Electrostatic interactions between ENaC's TMD2 and EMC6 are critical for their association, supporting a 'semi-insertase' model of membrane integration.
  • Bioinformatic analysis revealed over 200 multipass proteins with charged TMDs that may be clients of this electrostatic capture mechanism.
  • EMC8 is crucial for EMC complex stability and function, a role not compensated by EMC9.

Conclusions:

  • The EMC employs a multifaceted mechanism involving insertase activity and chaperone-like stabilization for the biogenesis of multipass membrane proteins with hydrophilic TMDs.
  • Electrostatic interactions represent a key strategy for the EMC to handle unconventional hydrophilic transmembrane segments.
  • EMC8 plays a non-redundant role in EMC function, highlighting subunit-specific contributions to membrane protein biogenesis.