The assembly of nascent proteins into multi-subunit complexes is a tightly regulated process that must occur at high fidelity to maintain cellular homeostasis. The ER membrane protein complex (EMC) is an essential insertase that requires seven membrane-spanning and two soluble cytosolic subunits to function. Here, we show that the kinase with no lysine 1 (WNK1), known for its role in hypertension and neuropathy, functions as an assembly factor for the human EMC. WNK1 uses a conserved amphipathic helix to stabilize the soluble subunit, EMC2, by binding to the EMC2-8 interface. Shielding this hydrophobic surface prevents promiscuous interactions of unassembled EMC2 and directly competes for binding of E3 ubiquitin ligases, permitting assembly. Depletion of WNK1 thus destabilizes both the EMC and its membrane protein clients. This work describes an unexpected role for WNK1 in protein biogenesis and defines the general requirements of an assembly factor that will apply across the proteome.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254792 | PMC |
| http://dx.doi.org/10.1016/j.molcel.2021.04.013 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression.
Front Med
January 2025
Guizhou University Medical College, Guiyang, 550025, China.
The p60 subunit of the chromatin assembly factor-1 complex, that is, chromatin assembly factor-1 subunit B (CHAF1B), is a histone H3/H4 chaperone crucial for the transcriptional regulation of cell differentiation and self-renewal. CHAF1B is overexpressed in several cancers and may represent a potential target for cancer therapy. However, its expression and clinical significance in lung squamous-cell carcinoma (LUSC) remain unclear.
View Article and Find Full Text PDFStructure and assembly mechanisms of the microbial community on an artificial reef surface, Fangchenggang, China.
Appl Microbiol Biotechnol
January 2025
Key Laboratory of Marine Ranching, Ministry of Agriculture and Rural Affairs, China, South China Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Guangzhou, 510300, China.
The construction of artificial reefs (ARs) is an effective way to restore habitats and increase and breed fishery resources in marine ranches. However, studies on the impacts of ARs on the structure, function, and assembly patterns of the bacterial community (BC), which is important in biogeochemical cycles, are lacking. The compositions, diversities, assembly patterns, predicted functions, and key environmental factors of the attached and free-living microbial communities in five-year ARs (O-ARs) and one-year ARs (N-ARs) in Fangchenggang, China, were analyzed via 16S rRNA gene sequencing.
View Article and Find Full Text PDFRole of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates.
Viruses
January 2025
Department of Medicine, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization.
View Article and Find Full Text PDFDecrease in HBsAg After TAF Switching from Entecavir During Long-Term Treatment of Chronic Hepatitis B Virus Infection.
Viruses
December 2024
Third Department of Internal Medicine, Faculty of Medicine, Academic Assembly, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Achieving HBsAg seroclearance is a key goal in treating chronic hepatitis B virus (HBV) infection but remains difficult with nucleos(t)ide analogues (NAs). Tenofovir alafenamide fumarate (TAF), a recommended NA for managing chronic HBV infection (CHB), has uncertain effects on HBsAg levels and potential adverse events when used long-term after switching from entecavir (ETV). We retrospectively evaluated 77 CHB patients, including 47 who switched from ETV to TAF with a median follow-up of 40 months post-switch and a median of 60 months of HBsAg monitoring pre-switch.
View Article and Find Full Text PDFHost RNA-Binding Proteins as Regulators of HIV-1 Replication.
Viruses
December 2024
Laboratory of Molecular and Cellular Virology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago 8380453, Chile.
RNA-binding proteins (RBPs) are cellular factors involved in every step of RNA metabolism. During HIV-1 infection, these proteins are key players in the fine-tuning of viral and host cellular and molecular pathways, including (but not limited to) viral entry, transcription, splicing, RNA modification, translation, decay, assembly, and packaging, as well as the modulation of the antiviral response. Targeted studies have been of paramount importance in identifying and understanding the role of RNA-binding proteins that bind to HIV-1 RNAs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!