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WNK1 is an assembly factor for the human ER membrane protein complex
Tino Pleiner1, Masami Hazu1, Giovani Pinton Tomaleri1
1Division of Biology and Biological Engineering, California Institute of Technology, 1200 E. California Blvd., Pasadena, CA 91125, USA.
Molecular Cell
|May 8, 2021
Summary
Kinase with no lysine 1 (WNK1) acts as a crucial assembly factor for the essential ER membrane protein complex (EMC). WNK1 stabilizes EMC subunits, preventing degradation and ensuring proper protein biogenesis for cellular homeostasis.
Area of Science:
- Cellular Biology
- Protein Biogenesis
- Molecular Mechanisms
Background:
- Protein complex assembly is vital for cellular homeostasis.
- The ER membrane protein complex (EMC) is essential for protein insertion.
- The EMC comprises seven membrane-spanning and two soluble cytosolic subunits.
Purpose of the Study:
- To investigate the role of kinase with no lysine 1 (WNK1) in EMC assembly.
- To elucidate the molecular mechanism by which WNK1 facilitates EMC function.
- To understand the broader implications of WNK1 in protein biogenesis.
Main Methods:
- Depletion studies to assess WNK1's impact on EMC stability.
- Biochemical assays to analyze WNK1's interaction with EMC subunits.
- Structural analysis of WNK1's binding interface with EMC2.
Main Results:
- WNK1 functions as an assembly factor for the human EMC.
- WNK1 stabilizes the soluble EMC2 subunit via a conserved amphipathic helix.
- WNK1 binding prevents promiscuous interactions and E3 ubiquitin ligase binding, promoting assembly.
- WNK1 depletion destabilizes the EMC and its client membrane proteins.
Conclusions:
- WNK1 plays an unexpected but critical role in protein biogenesis.
- WNK1 acts as a dedicated assembly factor for the EMC complex.
- The findings define general requirements for assembly factors applicable across the proteome.
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