Affinage

Showing LDAF1 — TMEM159 is a alias.

LDAF1

Lipid droplet assembly factor 1 · UniProt Q96B96

Length
161 aa
Mass
17.5 kDa
Annotated
2026-06-10
15 papers in source corpus 6 papers cited in narrative 6 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

LDAF1 (promethin/TMEM159) is a core component of the lipid droplet (LD) biogenesis machinery that, together with seipin, determines where LDs form in the endoplasmic reticulum (PMID:31708432). LDAF1 and seipin assemble into an ~600 kDa oligomeric complex—the lipid droplet assembly complex (LDAC)—that copurifies with triacylglycerol (TG), and in the absence of LDAF1 LDs form only at substantially higher cellular TG concentrations, establishing LDAF1 as rate-determining for LD nucleation (PMID:31708432). Structurally, LDAF1 forms a central ring within a seipin cage to create a toroidal, membrane-spanning chamber that excludes phospholipids while admitting TG, where TG contacts LDAF1 to nucleate an oil phase; the reconstituted LDAC is both necessary and sufficient to drive oil-phase separation below the threshold of spontaneous phase separation (PMID:40832250). Recruitment of LDAF1 to the complex is promoted by TAG occupancy of seipin's luminal helices, such that a seipin mutant compromised for TAG trapping colocalizes poorly with LDAF1 (PMID:33481779). Once an LD forms, LDAF1 dissociates from seipin and relocates to the nascent LD surface, and redirecting LDAF1 to ectopic membranes co-recruits seipin and reroutes LD formation to those sites (PMID:31708432). This function is evolutionarily conserved, with homologs in Drosophila and yeast decorating LDs and partnering with seipin to control LD size, number, and lipid storage (PMID:33307187).

Mechanistic history

Synthesis pass · year-by-year structured walk · 5 steps
  1. 2019 High

    Established LDAF1 as a physical seipin partner and a site-determining factor for LD biogenesis, answering where and how LDs are nucleated in the ER.

    Evidence Co-purification of an ~600 kDa TG-containing complex, plasma-membrane re-localization rescue, and loss-of-function with quantitative LD readout in cells

    PMID:30901948 PMID:31708432

    Open questions at the time
    • Did not define the structural architecture of the complex
    • Mechanism of TG-driven nucleation not resolved
  2. 2020 Medium

    Demonstrated the LD-biogenesis role of LDAF1-family proteins is evolutionarily conserved beyond mammalian cells.

    Evidence Localization, seipin interaction, and gain/loss-of-function LD phenotyping of the Drosophila homolog CG32803 in cells and in vivo

    PMID:33307187

    Open questions at the time
    • Conservation of the precise molecular mechanism not tested
    • Structural basis of fly seipin–LDAF1 association not resolved
  3. 2021 Medium

    Linked LDAF1 recruitment to seipin's TAG-handling, showing that lipid substrate occupancy shapes the LDAF1 binding interface.

    Evidence Molecular dynamics simulations bridged to cell-based colocalization with the TAG-trapping-deficient seipin S166D mutant

    PMID:33481779

    Open questions at the time
    • Direct biochemical measurement of TAG-dependent affinity not provided
    • Single-lab computational/cell approach
  4. 2025 High

    Resolved the mechanism by which the LDAC nucleates oil-phase separation, defining LDAF1 as a central ring within a seipin cage forming a TG-selective chamber.

    Evidence In vitro reconstitution with purified LDAC and defined membranes, structural studies, MD simulations and biochemical assays (preprint)

    PMID:40832250

    Open questions at the time
    • Preprint, not yet peer-reviewed
    • How LDAF1 dissociation and LD-surface relocation is triggered not mechanistically defined
  5. 2025 Medium

    Showed the seipin–LDAF1 scaffold is pre-assembled and remodeled by neutral lipid availability, addressing the dynamics of complex assembly.

    Evidence In vivo site-specific photo-crosslinking of the yeast homolog Ldo45 with metabolic manipulation of neutral lipid synthesis (preprint)

    PMID:bio_10.1101_2025.03.14.642698

    Open questions at the time
    • Findings in yeast ortholog; relevance to human LDAF1 inferred
    • Preprint, not yet peer-reviewed

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular trigger that releases LDAF1 from seipin and drives its relocation to the nascent LD surface remains undefined.
  • No biochemical signal or conformational switch identified for LDAF1 dissociation
  • Post-LD-surface function of LDAF1 uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008289 lipid binding 2
Localization
GO:0005811 lipid droplet 3 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-1430728 Metabolism 2 R-HSA-1852241 Organelle biogenesis and maintenance 1
Partners
SEIPIN/BSCL2
Complex memberships
lipid droplet assembly complex (LDAC; seipin-LDAF1)

Evidence

Reading pass · 6 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2019 LDAF1 (TMEM159/promethin) physically interacts with seipin to form an ~600 kDa oligomeric complex that copurifies with triacylglycerol (TG). LDs form at LDAF1-seipin complexes, and re-localization of LDAF1 to the plasma membrane co-recruits seipin and redirects LD formation to those sites. Once LDs form, LDAF1 dissociates from seipin and moves to the LD surface. In the absence of LDAF1, LDs form only at significantly higher cellular TG concentrations, establishing LDAF1 as a core component of the LD biogenesis machinery that determines sites of LD formation in the ER. Co-purification/biochemical reconstitution of ~600 kDa complex, re-localization experiments (plasma membrane targeting), loss-of-function analysis, live imaging of LD formation sites Developmental cell High 31708432
2019 Promethin (LDAF1/TMEM159) forms a complex with seipin, and its localization to the LD surface can be modulated by seipin expression levels, identifying it as a novel seipin partner protein associated with the LD surface. Co-immunoprecipitation, fluorescence microscopy/localization studies, seipin overexpression/depletion Cells Medium 30901948
2021 Association of nascent wild-type seipin complexes with promethin (LDAF1) is promoted by TAGs; the S166D seipin mutant (which compromises TAG trapping at the luminal α3 helix) colocalizes poorly with promethin, indicating that TAG occupancy within the seipin ring creates a favorable LDAF1 binding interface. Molecular dynamics simulations bridged to cell-based colocalization experiments; seipin point mutant (S166D) analysis PLoS biology Medium 33481779
2020 CG32803 (dmLDAF1), the Drosophila melanogaster homolog of LDAF1, decorates LDs in cultured cells and in vivo and is physically linked to fly and mouse seipin proteins. Altering dmLDAF1 abundance affects LD size, number, and overall lipid storage amounts, demonstrating an evolutionarily conserved function for LDAF1-family proteins in LD biogenesis. Fluorescence microscopy (LD decoration in cells and in vivo), protein interaction assays (linking to seipin), gain- and loss-of-function with quantitative LD phenotype readout Insect biochemistry and molecular biology Medium 33307187
2025 The lipid droplet assembly complex (LDAC), composed of seipin and LDAF1, was reconstituted in vitro with purified components and membranes containing physiological TG levels, demonstrating that the LDAC is both necessary and sufficient to catalyze oil-phase formation below the threshold of spontaneous phase separation. Structural studies reveal that LDAF1 forms a central ring within a seipin cage, creating a toroidal, membrane-spanning structure. Molecular dynamics simulations and biochemical assays show this structure forms a selective chamber that limits phospholipids but allows TG access, where TG interacts with LDAF1 to nucleate an oil phase and initiate LD formation. In vitro reconstitution with purified LDAC and defined membranes; structural studies (cryo-EM implied); molecular dynamics simulations; biochemical assays bioRxivpreprint High 40832250
2025 In yeast, the Ldo45 protein (yeast homolog of human LDAF1) resides at the center of the seipin ring both in the absence and presence of neutral lipids, as shown by in vivo site-specific photo-crosslinking. Neutral lipid synthesis leads to recruitment of Ldo45 (but not Ldo16) to the seipin complex, suggesting the complex is a pre-assembled scaffold remodeled in response to increased neutral lipid availability. In vivo site-specific photo-crosslinking approach; genetic/metabolic manipulation of neutral lipid synthesis bioRxivpreprint Medium bio_10.1101_2025.03.14.642698

Source papers

Stage 0 corpus · 15 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 LDAF1 and Seipin Form a Lipid Droplet Assembly Complex. Developmental cell 181 31708432
2021 Seipin traps triacylglycerols to facilitate their nanoscale clustering in the endoplasmic reticulum membrane. PLoS biology 73 33481779
2019 Promethin Is a Conserved Seipin Partner Protein. Cells 59 30901948
2020 Lipid droplet biogenesis: A mystery "unmixing"? Seminars in cell & developmental biology 54 32192830
2004 Identification of promethin and PGLP as two novel up-regulated genes in PPARgamma1-induced adipogenic mouse liver. Biochimie 28 15589683
2024 A metabolically controlled contact site between vacuoles and lipid droplets in yeast. Developmental cell 26 38367622
2018 Human brain arousal in the resting state: a genome-wide association study. Molecular psychiatry 26 29703947
2020 New friends for seipin - Implications of seipin partner proteins in the life cycle of lipid droplets. Seminars in cell & developmental biology 22 32402516
2020 CG32803 is the fly homolog of LDAF1 and influences lipid storage in vivo. Insect biochemistry and molecular biology 11 33307187
2021 The unique genome organization of two novel fusariviruses hosted by the true morel mushroom Morchella esculenta. Virus research 6 34146607
2019 LDAF1 Holds the Key to Seipin Function. Developmental cell 5 31794714
2009 Identification and tissue-specific expression of a promethin-like homolog in amphioxus Branchiostoma belcheri. Molecular biology reports 4 19685162
2024 The Vacuole Lipid Droplet Contact Site vCLIP. Contact (Thousand Oaks (Ventura County, Calif.)) 3 39717764
2025 Mechanism for oil-phase separation by the lipid droplet assembly complex. bioRxiv : the preprint server for biology 1 40832250
2025 Jack of all trades - the lipid droplet organization (LDO) proteins are multifunctional organelle surface receptors. Biological chemistry 0 41400403

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