Related Experiment Video
Updated: Aug 24, 2025

10:43
Single-Molecule Diffusion and Assembly on Polymer-Crowded Lipid Membranes
Published on: July 19, 2022
2.4K
Substrate-driven assembly of a translocon for multipass membrane proteins
Arunkumar Sundaram1, Melvin Yamsek1, Frank Zhong2
1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA.
Nature
|October 19, 2022
Summary
Researchers identified a specialized
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Biogenesis
Background:
- Most membrane proteins are synthesized on endoplasmic reticulum (ER)-bound ribosomes at the translocon.
- The mechanism by which the translocon accommodates diverse substrates is poorly understood.
Purpose of the Study:
- To define the composition, function, and assembly of a translocon specialized for multipass membrane protein biogenesis.
- To elucidate how nascent multipass proteins recruit this specialized translocon.
Main Methods:
- Analysis of insertion intermediates.
- Reconstitution studies.
- Analysis of cells lacking multipass translocon components.
Main Results:
- Identified a 'multipass translocon' composed of GET- and EMC-like (GEL), protein associated with translocon (PAT), and back of Sec61 (BOS) complexes.
- Nascent chain features trigger multipass translocon assembly.
- Multipass translocon components are crucial for protein topogenesis and stability.
Conclusions:
- Established the mechanism of selective multipass translocon recruitment by nascent multipass proteins.
- The ER translocon is a dynamic assembly that adjusts subunit composition co-translationally.
- This dynamic assembly accommodates diverse substrate biosynthetic needs.
Related Concept Videos
Insertion of Multi-pass Transmembrane Proteins in the RER
8.2K
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...
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...
8.2K
Protein Translocation Machinery on the ER Membrane
4.8K
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...
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...
4.8K
Cotranslational Protein Translocation
7.5K
Translocation of proteins across membranes is an ancient process that occurs even in bacteria and archaebacteria. In fact, the components of the translocation machinery are still conserved between prokaryotes and eukaryotes.
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
Sec61 channel partners for cotranslational translocation
During cotranslational translocation, the Sec61 channel partners with the signal recognition particle (SRP), the signal recognition particle receptor (SR), and the ribosomes to transport the nascent polypeptide chain...
7.5K
Protein Transport into the Inner Mitochondrial Membrane
4.1K
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...
Transport of mitochondrial precursors across the TIM23 channel is driven by...
4.1K
Translocation of Proteins into the Mitochondria
3.2K
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
3.2K
Protein Transport to the Stroma
1.9K
Chloroplasts are triple membrane structures with an outer membrane, an inner membrane, and a thylakoid membrane, each containing distinct metabolite transporters, membrane translocons, and enzymes. Appropriate sorting and translocating these proteins to their correct membrane systems is essential for chloroplast function.
Protein complexes called the translocon of the outer chloroplast membrane or TOC complex, and the translocon of the inner chloroplast membrane or TIC complex mediate the...
Protein complexes called the translocon of the outer chloroplast membrane or TOC complex, and the translocon of the inner chloroplast membrane or TIC complex mediate the...
1.9K

