Transmembrane Domain Recognition during Membrane Protein Biogenesis and Quality Control

@article{Guna2018TransmembraneDR,
  title={Transmembrane Domain Recognition during Membrane Protein Biogenesis and Quality Control},
  author={Alina Guna and Ramanujan S. Hegde},
  journal={Current Biology},
  year={2018},
  volume={28},
  pages={R498-R511}
}

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References

SHOWING 1-10 OF 148 REFERENCES

Tail-anchored membrane protein insertion into the endoplasmic reticulum

A recently discovered post-translational pathway using an entirely different set of factors involving transmembrane domain (TMD)-selective cytosolic chaperones and an accompanying receptor at the ER is discovered.

Protein translocation across the eukaryotic endoplasmic reticulum and bacterial plasma membranes

Structural, genetic and biochemical data show how the channel opens across the membrane, releases hydrophobic segments of membrane proteins laterally into lipid, and maintains the membrane barrier for small molecules.

The signal recognition particle and its interactions during protein targeting.

Membrane protein insertion at the endoplasmic reticulum.

  • S. ShaoR. Hegde
  • Biology
    Annual review of cell and developmental biology
  • 2011
The conceptual and mechanistic themes underlying these core membrane protein insertion pathways, the complexities that challenge the authors' understanding, and future directions to overcome these obstacles are reviewed.

Mechanisms of Tail-Anchored Membrane Protein Targeting and Insertion.

These findings suggest how an interconnected network of targeting factors, cochaperones, and quality control machineries together ensures robust membrane protein biogenesis.

Targeting pathways of C-tail-anchored proteins.

A Ribosome-Associating Factor Chaperones Tail-Anchored Membrane Proteins

The Bat3 complex acts as a TMD-selective chaperone that effectively channels TA proteins to the TRC40 insertion pathway, explaining their mislocalization in the analogous yeast deletion strains.

The Get1/2 transmembrane complex is an endoplasmic-reticulum membrane protein insertase

Light is shed on the fundamental point of convergence between co- translational and post-translational endoplasmic-reticulum membrane protein targeting and insertion: a mechanism for reducing the ability of a targeting factor to shield its substrates enables substrate handover to a transmembrane-domain-docking site embedded in the endoplASM-retICulum membrane.
...