Toxins (Basel)
The Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093 Warsaw, Poland.
Published: August 2019
Lysenin is a pore-forming toxin of the aerolysin family, which is derived from coelomic fluid of the earthworm . Upon binding to sphingomyelin (SM)-containing membranes, lysenin undergoes a series of structural changes promoting the conversion of water-soluble monomers into oligomers, leading to its insertion into the membrane and the formation of a lytic β-barrel pore. The soluble monomer and transmembrane pore structures were recently described, but the underlying structural details of oligomerization remain unclear. To investigate the molecular mechanisms controlling the conformational rearrangements accompanying pore formation, we compared the hydrogen-deuterium exchange pattern between lysenin and its mutant lysenin. This mutation arrests lysenin oligomers in the prepore state at the membrane surface and does not affect the structural dynamics of the water-soluble form of lysenin. In contrast, membrane-bound lysenin exhibited increased structural stabilization, especially within the twisted β-sheet of the N-terminal domain. We demonstrated that the structural stabilization of the lysenin prepore started at the site of lysenin's initial interaction with the lipid membrane and was transmitted to the twisted β-sheet of the N-terminal domain, and that lysenin was arrested in this conformation. In lysenin, stabilization of these regions drove the conformational changes necessary for pore formation.
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http://dx.doi.org/10.3390/toxins11080462 | DOI Listing |
Animal Model Exp Med
October 2024
Department of Orthopaedic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
This review compiles information from the literature on the chemical composition, pharmacological effects, and molecular mechanisms of earthworm extract (EE) and suggests possibilities for clinical translation of EE. We also consider future trends and concerns in this domain. We summarize the bioactive components of EE, including G-90, lysenin, lumbrokinase, antimicrobial peptides, earthworm serine protease (ESP), and polyphenols, and detail the antitumor, antithrombotic, antiviral, antibacterial, anti-inflammatory, analgesic, antioxidant, wound-healing, antifibrotic, and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies.
View Article and Find Full Text PDFAnalyst
July 2024
Department of Chemistry, Graduate School of Science, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
In biological membranes, lipids often interact with membrane proteins (MPs), regulating the localization and activity of MPs in cells. Although elucidating lipid-MP interactions is critical to comprehend the physiological roles of lipids, a systematic and comprehensive identification of lipid-binding proteins has not been adequately established. Therefore, we report the development of lipid-immobilized beads where lipid molecules were covalently immobilized.
View Article and Find Full Text PDFAdv Sci (Weinh)
May 2024
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
Earthworms, long utilized in traditional medicine, serve as a source of inspiration for modern therapeutics. Lysenin, a defensive factor in the coelom fluid of the earthworm Eisenia fetida, has multiple bioactivities. However, the inherent toxicity of Lysenin as a pore-forming protein (PFP) restricts its application in therapy.
View Article and Find Full Text PDFInt J Mol Sci
August 2023
Department of Physics, Boise State University, Boise, ID 83725, USA.
The intricate voltage regulation presented by lysenin channels reconstituted in artificial lipid membranes leads to a strong hysteresis in conductance, bistability, and memory. Prior investigations on lysenin channels indicate that the hysteresis is modulated by multivalent cations which are also capable of eliciting single-step conformational changes and transitions to stable closed or sub-conducting states. However, the influence on voltage regulation of Cu ions, capable of completely closing the lysenin channels in a two-step process, was not sufficiently addressed.
View Article and Find Full Text PDFJ Environ Sci (China)
November 2023
College of Resources and Environmental Sciences, China Agricultural University, Beijing 100193, China; Beijing Key Laboratory of Biodiversity and Organic Farming, Beijing 100193, China. Electronic address:
With increasing production of kitchen waste, cooking oil gradually enters the soil, where it can negatively affect soil fauna. In this study, we explored the effects of soybean oil on the survival, growth, reproduction, tissue structure, biochemical responses, mRNA expression, and gut microbiome of earthworms (Eisenia fetida). The median lethal concentration of soybean oil was found to be 15.
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