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Native Cell Membrane Nanoparticles System for Membrane Protein-Protein Interaction Analysis
Published on: July 16, 2020
Quality control of integral membrane proteins by assembly-dependent membrane integration
Matthias J Feige1, Linda M Hendershot
1Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. matthias.feige@stjude.org
Molecular Cell
|August 13, 2013
Summary
Cellular quality control mechanisms ensure proper membrane protein assembly in the endoplasmic reticulum (ER). Subunit interactions stabilize proteins by promoting membrane integration, preventing degradation of mislocalized transmembrane (TM) regions.
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Folding
Background:
- Cell-surface multiprotein complexes assemble in the endoplasmic reticulum (ER).
- Mechanisms of ER quality control for membrane protein biogenesis are not fully understood.
- Transmembrane (TM) proteins require proper integration and assembly for function.
Purpose of the Study:
- To investigate the quality control mechanisms governing membrane protein assembly in the ER.
- To determine how less hydrophobic TM regions are handled during protein biogenesis.
- To elucidate the role of subunit interactions in stabilizing membrane proteins.
Main Methods:
- Analysis of single-pass TM proteins with less hydrophobic TM regions.
- Utilized the αβT cell receptor (αβTCR) as a model system.
- Investigated the role of the Hsp70 chaperone BiP and specific subunit interactions.
Main Results:
- Less hydrophobic TM regions can mislocalize to the ER lumen and are recognized by BiP.
- Unassembled ER-lumenal subunits are rapidly degraded.
- Subunit interactions promote TM segment membrane integration, stabilizing the protein.
- A pivotal residue in the TCR α chain's TM region is critical for both ER import and assembly.
Conclusions:
- Membrane integration linked to protein assembly serves as a crucial quality control mechanism for membrane proteins.
- This process connects the ER's lumenal chaperone machinery to membrane protein biogenesis.
- Proper assembly and membrane integration are essential for preventing degradation of misfolded or mislocalized membrane proteins.
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