Equine lysozyme: the molecular basis of folding, self-assembly and innate amyloid toxicity.
Abstract: Calcium-binding equine lysozyme (EL) combines the structural and folding properties of c-type lysozymes and alpha-lactalbumins, connecting these two most studied subfamilies. The structural insight into its native and partially folded states is particularly illuminating in revealing the general principles of protein folding, amyloid formation and its inhibition. Among lysozymes EL forms one of the most stable molten globules and shows the most uncooperative refolding kinetics. Its partially-folded states serve as precursors for calcium-dependent self-assembly into ring-shaped and linear amyloids. The innate amyloid cytotoxicity of the ubiquitous lysozyme highlights the universality of this phenomenon and necessitates stringent measures for its prevention.
Publication Date: 2007-05-21 PubMed ID: 17531977DOI: 10.1016/j.febslet.2007.05.023Google Scholar: Lookup
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- Journal Article
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Summary
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This research explores the structure and folding properties of Equine Lysozyme (EL), a type of protein present in horses. It shows this protein’s ability to self-assemble into unique structures and its potential toxicity, and emphasizes the need for strategies to control this potentially dangerous process.
About Equine Lysozyme
- Equine lysozyme is a type of protein found in horses.
- This research focuses on its unique structural and folding properties.
- Notably, it has characteristics that connect it to two sets of proteins usually studied separately: c-type lysozymes and alpha-lactalbumins.
Understanding Protein Folding
- Details about the native state and partially folded states of Equine Lysozyme provide valuable insights about protein folding.
- This is extremely important because protein folding, the process by which a protein structure takes its functional shape or conformation, is fundamental to understanding biological functions and diseases.
Molecular Characteristics of Equine Lysozyme
- When it comes to lysozymes, Equine Lysozyme forms one of the most stable molten globules—intermediate forms that proteins assume while folding—and exhibits uncooperative refolding kinetics, meaning it doesn’t easily return to its original shape once unfolded.
- Under certain conditions, specifically the presence of calcium, this protein can self-assemble into unique structures known as ring-shaped and linear amyloids.
Innate Amyloid Cytotoxicity
- Amyloid formation, the molecular process by which proteins fold into a shape allowing them to stick together and form rigid fibres, is usually associated with certain type of diseases such as Alzheimer’s.
- When this process happens in cases where it shouldn’t, the amyloids formed can be toxic.
- This research highlights the innate amyloid cytotoxicity, or natural cell-damaging effect, of lysozymes such as Equine Lysozyme.
- Due to this potential harm, the researchers emphasize the crucial need for effective ways to prevent such toxicity.
Cite This Article
APA
Morozova-Roche LA.
(2007).
Equine lysozyme: the molecular basis of folding, self-assembly and innate amyloid toxicity.
FEBS Lett, 581(14), 2587-2592.
https://doi.org/10.1016/j.febslet.2007.05.023 Publication
Researcher Affiliations
- Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden. ludmilla.morozova-roche@medchem.umu.se
MeSH Terms
- Amyloid / chemistry
- Amyloid / toxicity
- Animals
- Calcium / metabolism
- Cell Survival / drug effects
- Horses
- Models, Molecular
- Muramidase / chemistry
- Muramidase / metabolism
- Neurons / cytology
- Neurons / drug effects
- Protein Binding
- Protein Folding
Citations
This article has been cited 8 times.- Jitaru SC, Neamtu A, Drochioiu G, Darie-Ion L, Stoica I, Petre BA, Gradinaru VR. A Diphenylalanine Based Pentapeptide with Fibrillating Self-Assembling Properties.. Pharmaceutics 2023 Jan 21;15(2).
- Woods KN, Pfeffer J. Using THz Spectroscopy, Evolutionary Network Analysis Methods, and MD Simulation to Map the Evolution of Allosteric Communication Pathways in c-Type Lysozymes.. Mol Biol Evol 2016 Jan;33(1):40-61.
- Vus K, Trusova V, Gorbenko G, Sood R, Kirilova E, Kirilov G, Kalnina I, Kinnunen P. Fluorescence Investigation of Interactions Between Novel Benzanthrone Dyes and Lysozyme Amyloid Fibrils.. J Fluoresc 2014 Mar;24(2):493-504.
- Clementi EA, Wilhelm KR, Schleucher J, Morozova-Roche LA, Hakansson AP. A complex of equine lysozyme and oleic acid with bactericidal activity against Streptococcus pneumoniae.. PLoS One 2013;8(11):e80649.
- Bruhn O, Grötzinger J, Cascorbi I, Jung S. Antimicrobial peptides and proteins of the horse--insights into a well-armed organism.. Vet Res 2011 Sep 2;42(1):98.
- Permyakov SE, Bakunts AG, Permyakova ME, Denesyuk AI, Uversky VN, Permyakov EA. Metal-controlled interdomain cooperativity in parvalbumins.. Cell Calcium 2009 Sep;46(3):163-75.
- Ashton L, Dusting J, Imomoh E, Balabani S, Blanch EW. Shear-induced unfolding of lysozyme monitored in situ.. Biophys J 2009 May 20;96(10):4231-6.
- Mendoza-Espinosa P, García-González V, Moreno A, Castillo R, Mas-Oliva J. Disorder-to-order conformational transitions in protein structure and its relationship to disease.. Mol Cell Biochem 2009 Oct;330(1-2):105-20.
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