Quality control of protein complex assembly by a transmembrane recognition 
factor.

Natarajan, N.; Foresti, O.; Wendrich, K.; Stein, A.; Carvalho, P.

doi:10.1016/j.molcel.2019.10.003

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Quality control of protein complex assembly by a transmembrane recognition factor.

MPS-Authors

/persons/resource/persons15866

Stein, A.
Research Group of Membrane Protein Biochemistry, MPI for Biophysical Chemistry, Max Planck Society;

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

3186899.pdf
(Publisher version), 3MB

Supplementary Material (public)

3186899_Suppl.zip
(Supplementary material), 23MB

Citation

Natarajan, N., Foresti, O., Wendrich, K., Stein, A., & Carvalho, P. (2020). Quality control of protein complex assembly by a transmembrane recognition factor. Molecular Cell, 77(1), 108-119. doi:10.1016/j.molcel.2019.10.003.

Cite as: https://hdl.handle.net/21.11116/0000-0005-7B2E-F

Abstract

The inner nuclear membrane (INM) is continuous with the endoplasmic reticulum (ER) but harbors a distinctive proteome essential for nuclear functions. In yeast, the Asi1/Asi2/Asi3 ubiquitin ligase complex safeguards the INM proteome through the clearance of mislocalized ER membrane proteins. How the Asi complex selectively targets mislocalized proteins and coordinates its activity with other ER functions, such as protein biogenesis, is unclear. Here, we uncover a link between INM proteome identity and membrane protein complex assembly in the remaining ER. We show that lone proteins and complex subunits failing to assemble in the ER access the INM for Asi-mediated degradation. Substrates are recognized by direct binding of Asi2 to their transmembrane domains for subsequent ubiquitination by Asi1/Asi3 and membrane extraction. Our data suggest a model in which spatial segregation of membrane protein complex assembly and quality control improves assembly efficiency and reduces the levels of orphan subunits.