An anomalous abundance of tryptophan residues in ceramide synthases based on analysis of all membrane proteins in the Swiss-Prot database.

The relationship between membrane proteins and the lipid constituents of the membrane bilayer depends on finely-tuned atomic interactions, which itself depends on the precise distribution of amino acids within the 3D structure of the protein. In this regard, tryptophan (Trp), one of the least abundant amino acids, is found at higher levels in transmembrane proteins where it likely plays a role in helping anchor them to the membrane. We now re-evaluate Trp distribution in membrane proteins using all known proteins in the Swiss-Prot database and confirm that it is somewhat higher (∼1.

Computational design and molecular dynamics simulations suggest the mode of substrate binding in ceramide synthases.

Until now, membrane-protein stabilization has relied on iterations of mutations and screening. We now validate a one-step algorithm, mPROSS, for stabilizing membrane proteins directly from an AlphaFold2 model structure. Applied to the lipid-generating enzyme, ceramide synthase, 37 designed mutations lead to a more stable form of human CerS2.

Rheumatoid arthritis and Hailey-Hailey disease treated with methotrexate.

We report a rare case of long-standing Hailey-Hailey disease in a Caucasian Portuguese 69-year-old woman, recently diagnosed with rheumatoid arthritis. The patient's skin lesions remained active and exudative despite topical and oral treatments with corticosteroids, tetracyclines, antifungals, and oral treatment with azathioprine. After introduction of methotrexate for rheumatoid arthritis treatment, the skin lesions regressed, with significant impact on the patient's quality of life.

Fatty acid transport protein 2 interacts with ceramide synthase 2 to promote ceramide synthesis.

Dihydroceramide is a lipid molecule generated via the action of (dihydro)ceramide synthases (CerSs), which use two substrates, namely sphinganine and fatty acyl-CoAs. Sphinganine is generated via the sequential activity of two integral membrane proteins located in the endoplasmic reticulum. Less is known about the source of the fatty acyl-CoAs, although a number of cytosolic proteins in the pathways of acyl-CoA generation modulate ceramide synthesis via direct or indirect interaction with the CerSs.

Ceramide synthases: Reflections on the impact of Dr. Lina M. Obeid.

Sphingolipids are a family of lipids that are critical to cell function and survival. Much of the recent work done on sphingolipids has been performed by a closely-knit family of sphingolipid researchers, which including our colleague, Dr. Lina Obeid, who recently passed away.

Biophysical Analysis of Lipid Domains in Mammalian and Yeast Membranes by Fluorescence Spectroscopy.

The use of steady-state and time-resolved fluorescence spectroscopy to study sterol and sphingolipid-enriched lipid domains as diverse as the ones found in mammalian and fungal membranes is herein described. We first address how to prepare liposomes that mimic raft-containing membranes of mammalian cells and how to use fluorescence spectroscopy to characterize the biophysical properties of these membrane model systems. We further illustrate the application of Förster resonance energy transfer (FRET) to study nanodomain reorganization upon interaction with small bioactive molecules, phenolic acids, an important group of phytochemical compounds.

Ceramide Domains in Health and Disease: A Biophysical Perspective.

Ceramides are the central molecules in sphingolipid metabolism. In addition, they are recognized as important modulators of cell function, playing key roles in several cellular processes that range from cell proliferation to cell death. Moreover, ceramides were implicated in multiple diseases, including cancer, neurodegenerative and metabolic diseases, and also in infection by different pathogens.