Biology subjects

Basile, M.

Publications and source records attributed to Basile, M..

3 recordsLinked to original sources

bioRxiv2025

A computational analysis of the glycoprotein LRP1 structure and the role of glycans as quaternary glue

The low-density lipoprotein receptor-related protein 1 (LRP1) plays a critical role in development and transport across the blood-brain barrier (BBB), yet until now, its molecular architecture remained unresolved due to the absence of an experimentally determined structure. Using homology modeling and neural network-based structure prediction algorithms, complemented with molecular dynamics (MD) simulations, we propose a comprehensive model of LRP1 structures. We observe a natural dimerization mechanism and provide insight into the dynamic behavior of its flexible domains under physiological conditions. We investigated the stability of non-covalent interactions keeping LRP1s and {beta} chains linked together, and found the energy required to break the link is 180{+/-}2 kT. The MD characterization highlights the fundamental role of glycans in the creation of LRP1s quaternary structure, increasing the number of intra-dimeric contacts. This study opens new avenues for targeted drug design strategies, enhancing our molecular understanding of LRP1s receptor-mediated transport in the brain and the key mediation of glycosylation in protein-protein interactions.

biophysics↗

bioRxiv2024

Evolutionary and Functional Analysis of Monoamine Oxidase C (MAO C): A Novel Member of the MAO Gene Family

The monoamine oxidase (MAO) gene family encodes for enzymes that perform the oxidative deamination of monoamines, a process required to degrade norepinephrine, serotonin, dopamine, and other amines. While mammalian MAO enzymes, MAO A and MAO B, have been extensively studied, the molecular properties of the other family members are only partly uncovered. This study aims to explore the evolution of monoamine oxidases, emphasizing understanding the MAO gene repertoire among vertebrates. Our analyses show that the duplication that gave rise to MAO A and MAO B occurred in the ancestor of tetrapods, between 408 and 352 million years ago. Non-tetrapod jawed vertebrates possess the ancestral preduplicative condition of MAO A/B. Our results also identified a new family member, MAO C, in non-tetrapod jawed vertebrates. Thus, most jawed vertebrates possess a repertoire of two MAO genes, MAO A and MAO B in tetrapods and MAO A/B and MAO C in non-tetrapod jawed vertebrates, representing different MAO gene lineages. Jawless vertebrates possess the ancestral condition of a single copy gene, MAO A/B/C. Enzymatic assays conducted on the MAO recombinant enzymes of the Indo-Pacific tarpon show that both proteins, MAO A/B and MAO C, have enzymatic and molecular properties more similar to human MAO A, with the former featuring a strikingly higher activity rate when compared to all other MAO enzymes. Our analyses underscore the importance of scanning the tree of life for new gene lineages to understand phenotypic diversity and gain detailed insights into their function.

evolutionary biology↗

bioRxiv2020

Species associations and management intensity modulate the habitat niche breadth of forest birds

Species associations can have profound effects on the realized habitat niche of species, indicating that habitat structure alone cannot fully explain observed abundances. To account for this aspect of community organization in niche modelling, we developed multi-species abundance models, incorporating the local effect of potentially associated species, alongside with environmental ones, targeting mainly forest management intensity. We coupled it with a landscape-scale analysis to further examine the role of management intensity in modifying the habitat niche in connection with the landscape context. Using empirical data from the Black Forest in southern Germany, we focused on the forest bird assemblage and in particular on the cavity nester and canopy forager guilds. We included in the analysis species that co-occur and for which evidences suggest association is likely. Our findings show that the local effect of species associations can moderate the effects of management intensity. We also found that species express a larger habitat niche breadth in intensively managed forests, depending on the landscape context. Species associations may facilitate the utilization of a broader range of environmental conditions under intensive forest management, which benefits some species over others. Such network of associations may be a relevant factor in the effectiveness of conservation-oriented forest management.

ecology↗