AI Article Synopsis
Article Abstract
Polymers can facilitate detergent-free extraction of membrane proteins into nanodiscs (e.g., SMALPs, DIBMALPs), incorporating both integral membrane proteins as well as co-extracted native membrane lipids. Lipid-only SMALPs and DIBMALPs have been shown to possess a unique property; the ability to exchange lipids through 'collisional lipid mixing'. Here we expand upon this mixing to include protein-containing DIBMALPs, using the rhomboid protease GlpG. Through lipidomic analysis before and after incubation with DMPC or POPC DIBMALPs, we show that lipids are rapidly exchanged between protein and lipid-only DIBMALPs, and can be used to identify bound or associated lipids through 'washing-in' exogenous lipids. Additionally, through the requirement of rhomboid proteases to cleave intramembrane substrates, we show that this mixing can be performed for two protein-containing DIBMALP populations, assessing the native function of intramembrane proteolysis and demonstrating that this mixing has no deleterious effects on protein stability or structure.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11364529 | PMC |
| http://dx.doi.org/10.1038/s41467-024-51989-0 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
4-Oxo-β-lactams as Covalent Inhibitors of the Mitochondrial Intramembrane Protease PARL.
ACS Med Chem Lett
December 2024
Laboratory of Chemical Biology, Department of Cellular and Molecular Medicine, KU Leuven - University of Leuven, Herestraat 49 box 901b, 3000 Leuven, Belgium.
Rhomboid proteases play a variety of physiological roles, but rhomboid protease inhibitors have been mostly developed for the model rhomboid GlpG. In this work, we screened different electrophilic scaffolds against the human mitochondrial rhomboid PARL and found 4-oxo-β-lactams as submicromolar inhibitors. Multifaceted computations suggest explanations for the activity at the molecular scale and provide models of covalently bound complexes.
View Article and Find Full Text PDFRhomboid-like 2 correlated with TME infiltration inhibits cuproptosis-related genes and drives malignant phenotype in clear cell renal cell carcinoma.
Sci Rep
November 2024
Department of Urology, The First Affiliated Hospital of Hainan Medical University, No. 31 Longhua Road, Longhua District, Haikou, 570102, Hainan Province, China.
The crosstalk between cuproptosis and the tumor immune microenvironment (TIME) is vital during clear cell renal cell carcinoma (ccRCC) malignant progression. However, the underlying molecular mechanisms regulate this cross-talk remain elusive. Through tailored machine learning, we analyze clinical ccRCC data from The Cancer Genome Atlas (TCGA) to explore the critical factors that regulate the interaction among cuproptosis, TIME, and tumor progression.
View Article and Find Full Text PDFEvaluating the impact of the membrane thickness on the function of the intramembrane protease GlpG.
Biophys J
December 2024
Institute for Medical Physics and Biophysics, University of Leipzig, Leipzig, Germany. Electronic address:
Cellular membranes exhibit a huge diversity of lipids and membrane proteins that differ in their properties and chemical structure. Cells organize these molecules into distinct membrane compartments characterized by specific lipid profiles and hydrophobic thicknesses of the respective domains. If a hydrophobic mismatch occurs between a membrane protein and the surrounding lipids, there can be functional consequences such as reduced protein activity.
View Article and Find Full Text PDFThe Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi.
Nat Commun
October 2024
Institute of Molecular Biochemistry, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
The Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex uses its rhomboid pseudo-protease subunit, Dsc2, to assess the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex likely interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation.
View Article and Find Full Text PDFRhomboid proteases are ubiquitous intramembrane serine proteases that can cleave transmembrane substrates within lipid bilayers. They exhibit many and diverse functions, such as but not limited to, growth factor signaling, immune and inflammatory response, protein quality control, and parasitic invasion. Human rhomboid protease RHBDL4 has been demonstrated to play a critical role in removing misfolded proteins from the Endoplasmic Reticulum and is implicated in severe diseases such as various cancers and Alzheimer's disease.
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!