ArticleProceedings of the National Academy of Sciences of the United States of America2018
Proteomic analysis of monolayer-integrated proteins on lipid droplets identifies amphipathic interfacial α-helical membrane anchors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Alternative organelle targeting of OPA1 mediates fatty acid release from lipid droplets.bioRxiv : the preprint server for biology · 2026Article
- Navigating lipid droplet proteins - part I: ER targeting routes of lipid droplet-destined membrane proteins.Biochemical Society transactions · 2025Review
- Selenoprotein K at the intersection of cellular pathways.Archives of biochemistry and biophysics · 2025Review
- Feedback regulation of retinaldehyde reductase DHRS3, a critical determinant of retinoic acid homeostasis.FEBS letters · 2025Article
- The Lipid Droplet Protein DHRS3 Is a Regulator of Melanoma Cell State.Pigment cell & melanoma research · 2025Article
- Interplay between lipid droplets and alpha-synuclein: implication in Parkinson's disease pathogenesis.Frontiers in molecular neuroscience · 2025Review
- Roles of lipid droplets and related proteins in metabolic diseases.Lipids in health and disease · 2024Review
- Rab1b facilitates lipid droplet growth by ER-to-lipid droplet targeting of DGAT2.Science advances · 2024Article
- Hairpin protein partitioning from the ER to lipid droplets involves major structural rearrangements.Nature communications · 2024Article
- Hif1α/Dhrs3a Pathway Participates in Lipid Droplet Accumulation via Retinol and Ppar-γ in Fish Hepatocytes.International journal of molecular sciences · 2023Article
- An inducible amphipathic α-helix mediates subcellular targeting and membrane binding of RPE65.Life science alliance · 2023Article
- Coemergence of the Amphipathic Helix on Ameloblastin With Mammalian Prismatic Enamel.Molecular biology and evolution · 2022Article
- Identification of two pathways mediating protein targeting from ER to lipid droplets.Nature cell biology · 2022Article
- Co-translational biogenesis of lipid droplet integral membrane proteins.Journal of cell science · 2022Article
- Quantitative Proteomics and Differential Protein Abundance Analysis after the Depletion of PEX3 from Human Cells Identifies Additional Aspects of Protein Targeting to the ER.International journal of molecular sciences · 2021Article
- Complexity and Specificity of Sec61-Channelopathies: Human Diseases Affecting Gating of the Sec61 Complex.Cells · 2021Review
- Article
- Friend or Foe: Lipid Droplets as Organelles for Protein and Lipid Storage in Cellular Stress Response, Aging and Disease.Molecules (Basel, Switzerland) · 2020Review
- Triacylglycerols sequester monotopic membrane proteins to lipid droplets.Nature communications · 2020Article
- Partitioning of MLX-Family Transcription Factors to Lipid Droplets Regulates Metabolic Gene Expression.Molecular cell · 2020Article
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Authors and funding
9 authors.
Funding
Abstract
Despite not spanning phospholipid bilayers, monotopic integral proteins (MIPs) play critical roles in organizing biochemical reactions on membrane surfaces. Defining the structural basis by which these proteins are anchored to membranes has been hampered by the paucity of unambiguously identified MIPs and a lack of computational tools that accurately distinguish monolayer-integrating motifs from bilayer-spanning transmembrane domains (TMDs). We used quantitative proteomics and statistical modeling to identify 87 high-confidence candidate MIPs in lipid droplets, including 21 proteins with predicted TMDs that cannot be accommodated in these monolayer-enveloped organelles. Systematic cysteine-scanning mutagenesis showed the predicted TMD of one candidate MIP, DHRS3, to be a partially buried amphipathic α-helix in both lipid droplet monolayers and the cytoplasmic leaflet of endoplasmic reticulum membrane bilayers. Coarse-grained molecular dynamics simulations support these observations, suggesting that this helix is most stable at the solvent-membrane interface. The simulations also predicted similar interfacial amphipathic helices when applied to seven additional MIPs from our dataset. Our findings suggest that interfacial helices may be a common motif by which MIPs are integrated into membranes, and provide high-throughput methods to identify and study MIPs.
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