Related Experiment Video
Updated: Jun 1, 2026
05:52
Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
A conserved archaeal pathway for tail-anchored membrane protein insertion
John Sherrill1, Malaiyalam Mariappan, Pawel Dominik
1Department of Biochemistry & Molecular Biology, University of Chicago, Gordon Center for Integrative Science, Room W238, Chicago, IL 60637, USA.
Traffic (Copenhagen, Denmark)
|June 11, 2011
Summary
The TRC40 pathway, crucial for inserting tail-anchored membrane proteins into eukaryotic cells, is also present in archaea. This discovery reveals a broader evolutionary conservation of this essential protein insertion mechanism.
Area of Science:
- Biochemistry
- Molecular Biology
- Structural Biology
Background:
- Tail-anchored (TA) membrane proteins are essential in eukaryotes, inserted post-translationally via the TRC40 pathway into the endoplasmic reticulum.
- No comparable pathway had been identified in other life domains, limiting understanding of TA protein insertion evolution.
Purpose of the Study:
- To investigate the presence and function of TRC40 homologs in archaea.
- To elucidate the structural and mechanistic basis of TA protein insertion in non-eukaryotic organisms.
Main Methods:
- Determined the crystal structure of an archaebacterial TRC40 homolog bound to ADP•AlF(4)(-).
- Analyzed structural features, including zinc-mediated dimerization and hydrophobic grooves.
- Investigated interactions between archaeal TRC40 and transmembrane domains of TA substrates.
Main Results:
- The archaebacterial TRC40 homolog shares key structural features with its eukaryotic counterpart, including a zinc-mediated dimer and a hydrophobic groove.
- Archaeal TRC40 was shown to interact with the transmembrane domains of TA substrates.
- Archaeal TRC40 facilitates the membrane insertion of TA proteins.
Conclusions:
- The TRC40 pathway for tail-anchored membrane protein insertion is conserved across eukaryotes and archaea.
- This finding expands the known evolutionary scope of the TRC40 pathway.
- Suggests a more ancient origin for this fundamental membrane protein targeting mechanism.
Related Concept Videos
01:45Tail-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...
01:26Bacterial Translocation and Protein Secretion
Bacterial protein secretion involves translocation systems to ensure proteins reach their designated locations, including the plasma membrane, periplasm, outer membrane, or the external environment. These translocation systems are vital for bacterial physiology, supporting processes like membrane assembly, enzymatic activity in the periplasm, and interactions with the external environment. The division of labor between Sec and Tat pathways ensures efficiency in handling proteins with diverse...
01:20Cotranslational Protein Translocation
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...
01:39Mitochondrial Protein Sorting
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
01:22Protein Transport to the Thylakoids
Thylakoids are membrane-bound sac-like structures within the chloroplast that serve as sites for photosynthesis. Thylakoid lumen contains many electron transport proteins and is enclosed by a thylakoid membrane rich in the light-harvesting complex. Proteins targeted to the thylakoids are transported as precursors and are sorted by the general TOC/TIC import pathway. Once the precursor reaches the stroma, stromal processing peptidases remove their transit signal and expose thylakoid signal...
01:26Insertion 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...
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...