Related Experiment Video
Updated: May 31, 2026
05:52
Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
Structural basis for tail-anchored membrane protein biogenesis by the Get3-receptor complex
Susanne Stefer1, Simon Reitz, Fei Wang
1Institute for Biophysical Chemistry, Centre for Biomolecular Magnetic Resonance, Goethe University, D-60325 Frankfurt am Main, Germany.
Science (New York, N.Y.)
|July 2, 2011
Summary
This study reveals how tail-anchored proteins reach the endoplasmic reticulum membrane. The Get3 ATPase, along with the Get1/2 receptor, facilitates this crucial cellular delivery process.
Area of Science:
- Cell Biology
- Molecular Biology
- Structural Biology
Background:
- Tail-anchored (TA) proteins are essential for various cellular functions, including protein trafficking and apoptosis.
- Their C-terminal membrane anchor requires specific machinery for post-translational insertion into the endoplasmic reticulum (ER) membrane.
Purpose of the Study:
- To elucidate the structural basis of tail-anchored protein delivery to the ER membrane.
- To understand the mechanism of interaction between the Get3 ATPase and the Get1/2 receptor.
Main Methods:
- X-ray crystallography was used to determine the structures of Get3 in complex with Get1 and Get2.
- Biochemical experiments were performed to validate structural findings and functional interactions.
Main Results:
- Crystal structures revealed Get3 complexed with Get1 and Get2 in distinct functional states.
- Get1 and Get2 bind to Get3 at adjacent, overlapping sites, with simultaneous binding possible.
- Complex formation induces conformational changes in Get3 necessary for TA protein insertion.
Conclusions:
- The Get1/2 receptor complex facilitates TA protein delivery by interacting with Get3.
- Structural and biochemical data suggest a molecular mechanism for nucleotide-regulated TA protein insertion into the ER membrane.
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...
01:26Insertion 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...
01:29GPI Anchoring of Proteins in the ER Membrane
GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
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...
01:28Protein 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.
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.
01:21Structure of Porins
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel precursors...