Sabbagh, B. | bioRxiv Science

bioRxiv2026

Comparison of the 4-helix bundle domains of perilipin 3 and perilipin 4 identifies features that contribute to lipid droplet binding

The perilipins generally represent the most abundant lipid droplet (LD) surface proteins in mammalian cells and can target LD subpopulations within the same cell. They are characterized by a conserved organization of disordered and folded regions, as well as a number of divergent features, which contribute to differences in perilipin function and LD targeting. Here, we focus on the C-terminal 4-helix bundle (4HB) domain that is present in all perilipins except for PLIN1. Using biochemical and in silico approaches, we show that the 4HB of PLIN3 is a stably folded domain and interacts with lipid surfaces in vitro and with LDs in model cells. The {beta}-subdomain at the bottom of the helical bundle is required for the binding to LDs, but not for the 4HB stability, suggesting that this region may promote direct interaction with the LD surface. In agreement, the 4HB of PLIN4, which does not contain an {beta}- subdomain, does not bind to LDs. Overall, our work shows that small differences in perilipin structural features impact their differential targeting to LDs.

biochemistry↗

bioRxiv2025

Perilipin 4 repetitive region forms amyloid fibrils promoted by a genetic expansion found in myopathy patients

Lipid-binding amphipathic proteins play key roles in cellular organization, yet their conformational flexibility makes them prone to aggregation. Here we study the aggregation of perilipin 4 (PLIN4), a protein of the lipid droplet (LD)-binding perilipin family. PLIN4 contains an unusually long ([~]1000 amino acid, aa) amphipathic helix composed of tandem 33-aa repeats, which folds on the LD surface. A genetic expansion that increases the number of repeats is associated with skeletal muscle dysfunction in patients suffering from a late-onset vacuolar myopathy (MRUPAV). We show that the genetic expansion and the precise sequence of the 33 aa repeats do not significantly alter PLIN4 interaction with LDs in cells. By contrast, purified fragments of the PLIN4 repetitive region form amyloid fibrils as characterized by cryo-EM and atomic force microscopy. Repeat expansion strongly accelerates fibril formation, consistent with enhanced self-assembly driven by the accumulation of identical repeats. PLIN4 aggregation is attenuated by the presence of LDs, indicating that lipid binding modulates the balance between membrane association and self-assembly. Together, these results establish PLIN4 as a previously unrecognized amyloid-forming protein and suggest that repeat expansion enhances amyloidogenic self-assembly, providing a foundation for future studies of its role in degenerative muscle disease.

biochemistry↗

bioRxiv2024

Visualization and quantification of coral reef soundscapes using CoralSoundExplorer software

Despite hosting some of the highest concentrations of biodiversity and providing invaluable goods and services in the oceans, coral reefs are under threat from global change and other local human impacts. Changes in living ecosystems often induce changes in their acoustic characteristics, but despite recent efforts in passive acoustic monitoring of coral reefs, rapid measurement and identification of changes in their soundscapes remains a challenge. Here we present the new open-source software CoralSoundExplorer (https://sound-scape-explorer.github.io/docs/CSE/), which is designed to study and monitor coral reef soundscapes. CoralSoundExplorer uses deep learning approaches and is designed to eliminate the need to extract conventional acoustic indices. To demonstrate CoralSoundExplorers functionalities, we use and analyze a set of recordings from three coral reef sites, each with different purposes (undisturbed site, tourist site and boat site) located on the island of Bora-Bora in French Polynesia. We explain the CoralSoundExplorer analysis workflow, from raw sounds to ecological results, detailing and justifying each processing step. We detail the software settings, the graphical representations used for visual exploration of soundscapes and their temporal dynamics, along with the analysis methods and metrics proposed. We demonstrate that CoralSoundExplorer is a powerful tool for identifying disturbances affecting coral reef soundscapes, combining visualizations of the spatio-temporal distribution of sound recordings with new quantification methods to characterize soundscapes at different temporal scales. Author summaryTodays scientists are faced with the challenge of analyzing large amounts of data, such as those generated by passive acoustic monitoring of ecosystems. We have built CoralSoundExplorer (https://sound-scape-explorer.github.io/docs/CSE/), an efficient tool for analyzing large datasets of sound recordings, which transforms coral reef soundscape recordings into visual representations in 2D or 3D spaces. By spreading them across easy-to-explore acoustic spaces, CoralSoundExplorer enables the observer to quickly grasp the characteristics of soundscapes, their differences and similarities, and their organization on different temporal scales. These acoustic spaces and their temporal dynamics can be quantified, for example to account for the speed at which soundscapes change over time. In this study, we take the example of reef soundscapes from the island of Bora-Bora to illustrate the features and possibilities offered by CoralSoundExplorer. CoralSoundExplorer is open source and easy to use, even for non-specialists, thanks to an interface that requires no coding skills. We provide detailed instructions for installing and using CoralSoundExplorer to help users get started easily. CoralSoundExplorer needs to be installed on a computer to perform the analyses and calculations based on sound recordings. There is also an online interface (https://sound-scape-explorer.github.io/coral-sound-explorer/) enabling users to visualize data that have already been processed by CoralSoundExplorer.

ecology↗