ArticleBiochimica et biophysica acta2013
The glycolipid transfer protein (GLTP) domain of phosphoinositol 4-phosphate adaptor protein-2 (FAPP2): structure drives preference for simple neutral glycosphingolipids.
Article in Biochimica et biophysica acta, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Use of Bicelle-Generated Lipid Bilayer Vesicle Nanoparticles for In Vitro Measurement of Lipid Intermembrane Transport.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Sphingolipid metabolism and regulated cell death in malignant melanoma.Apoptosis : an international journal on programmed cell death · 2024Review
- Whole-Genome Resequencing Highlights the Unique Characteristics of Kecai Yaks.Animals : an open access journal from MDPI · 2022Article
- Analysis of the Equilibrium Distribution of Ligands in Heterogeneous Media-Approaches and Pitfalls.International journal of molecular sciences · 2022Review
- Ceramide-1-phosphate transfer protein promotes sphingolipid reorientation needed for binding during membrane interaction.Journal of lipid research · 2022Article
- Emerging roles for human glycolipid transfer protein superfamily members in the regulation of autophagy, inflammation, and cell death.Progress in lipid research · 2020Review
- Up-regulation of glycolipid transfer protein by bicyclol causes spontaneous restriction of hepatitis C virus replication.Acta pharmaceutica Sinica. B · 2019Article
- Structural analyses of 4-phosphate adaptor protein 2 yield mechanistic insights into sphingolipid recognition by the glycolipid transfer protein family.The Journal of biological chemistry · 2018Article
- Functional evaluation of tryptophans in glycolipid binding and membrane interaction by HET-C2, a fungal glycolipid transfer protein.Biochimica et biophysica acta. Biomembranes · 2018Article
- How α-Helical Motifs Form Functionally Diverse Lipid-Binding Compartments.Annual review of biochemistry · 2017Review
- Phosphatidylserine Stimulates Ceramide 1-Phosphate (C1P) Intermembrane Transfer by C1P Transfer Proteins.The Journal of biological chemistry · 2017Article
- Sphingolipid transfer proteins defined by the GLTP-fold.Quarterly reviews of biophysics · 2015Article
- Modulation of hepatitis C virus genome replication by glycosphingolipids and four-phosphate adaptor protein 2.Journal of virology · 2014Article
- Arabidopsis accelerated cell death 11, ACD11, is a ceramide-1-phosphate transfer protein and intermediary regulator of phytoceramide levels.Cell reports · 2014Article
- Vesicular and non-vesicular transport feed distinct glycosylation pathways in the Golgi.Nature · 2013Article
- Ceramide-1-phosphate transfer protein (CPTP) regulation by phosphoinositides.The Journal of biological chemistryArticle
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Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Phosphoinositol 4-phosphate adaptor protein-2 (FAPP2) plays a key role in glycosphingolipid (GSL) production using its C-terminal domain to transport newly synthesized glucosylceramide away from the cytosol-facing glucosylceramide synthase in the cis-Golgi for further anabolic processing. Structural homology modeling against human glycolipid transfer protein (GLTP) predicts a GLTP-fold for FAPP2 C-terminal domain, but no experimental support exists to warrant inclusion in the GLTP superfamily. Here, the biophysical properties and glycolipid transfer specificity of FAPP2-C-terminal domain have been characterized and compared with other established GLTP-folds. Experimental evidence for a GLTP-fold includes: i) far-UV circular dichroism (CD) showing secondary structure with high alpha-helix content and a low thermally-induced unfolding transition (~41°C); ii) near-UV-CD indicating only subtle tertiary conformational change before/after interaction with membranes containing/lacking glycolipid; iii) Red-shifted tryptophan (Trp) emission wavelength maximum (λ(max)~352nm) for apo-FAPP2-C-terminal domain consistent with surface exposed intrinsic Trp residues; iv) 'signature' GLTP-fold Trp fluorescence response, i.e., intensity decrease (~30%) accompanied by strongly blue-shifted λ(max) (~14nm) upon interaction with membranes containing glycolipid, supporting direct involvement of Trp in glycolipid binding and enabling estimation of partitioning affinities. A structurally-based preference for other simple uncharged GSLs, in addition to glucosylceramide, makes human FAPP2-GLTP more similar to fungal HET-C2 than to plant AtGLTP1 (glucosylceramide-specific) or to broadly GSL-selective human GLTP. These findings along with the distinct mRNA exon/intron organizations originating from single-copy genes on separate human chromosomes suggest adaptive evolutionary divergence by these two GLTP-folds.
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