Covalent Blocking of Fibril Formation and Aggregation of Intracellular Amyloidgenic Proteins by Transglutaminase-Catalyzed Intramolecular Cross-Linking
| العنوان: | Covalent Blocking of Fibril Formation and Aggregation of Intracellular Amyloidgenic Proteins by Transglutaminase-Catalyzed Intramolecular Cross-Linking |
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| المؤلفون: | Takashi Konno, Shinichi Sato, Takashi Morii, Koji Ikura, Akiyoshi Hirata, Shigetoshi Oiki |
| المصدر: | Biochemistry. 44:2072-2079 |
| بيانات النشر: | American Chemical Society (ACS), 2005. |
| سنة النشر: | 2005 |
| مصطلحات موضوعية: | Adult, Intracellular Fluid, Repetitive Sequences, Amino Acid, Amyloid, Saccharomyces cerevisiae Proteins, Prions, Tissue transglutaminase, Guinea Pigs, Synucleins, Nerve Tissue Proteins, tau Proteins, Lactoglobulins, Protein aggregation, Fibril, Biochemistry, Catalysis, chemistry.chemical_compound, Protein structure, Animals, Humans, Alpha-synuclein, Transglutaminases, biology, Peptide Fragments, Protein Structure, Tertiary, Cross-Linking Reagents, chemistry, Intramolecular force, Chromatography, Gel, alpha-Synuclein, biology.protein, Cattle, Thioflavin, Peptide Termination Factors |
| الوصف: | Two different types of physical bonding have been proposed to involve in the formation of neuronal inclusions of patients with neurodegenerative diseases such as Alzheimer's, Parkinson's, and polyglutamine diseases. One is the noncovalent bonding that stabilizes the amyloid-type fibrous aggregates, and the other is the covalent cross-linking catalyzed by tissue transglutaminase. The cross-linking is subdivided into the inter- and intramolecular cross-linking. Little attention has been paid to the pathological roles of the intramolecular cross-linking. To elucidate the possible interplay between the intramolecular cross-linking and the amyloid-type fibril formation, we performed an in vitro aggregation analysis of three intracellular amyloidgenic proteins (a domain of tau protein, alpha-synuclein, and truncated yeast prion Sup35) in the presence of tissue transglutaminase. The analysis was performed in low concentrations of the proteins using techniques including thioflavin T binding and mass spectrometry. The results demonstrated that the amyloid-type fibril formation was strongly inhibited by the transglutaminase-catalyzed intramolecular cross-linking, which blocked both the nucleation and the fiber extension steps of the amyloid formation. Far-UV CD spectroscopy indicated that the cross-linking slightly altered the backbone conformation of the proteins. It is likely that conformational restriction imposed by the intramolecular cross-links has impaired the ordered assembly of the amyloidgenic proteins. Nonamyloid type aggregation was also suppressed by the intramolecular cross-links. On the basis of the results, we proposed that tissue transglutaminase is a modulator for the protein aggregation and can act defensively against the fibril deposition in neurons. |
| تدمد: | 1520-4995 0006-2960 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::82ac81bf80e6c3fd45c84e28b01e5101Test https://doi.org/10.1021/bi047722dTest |
| رقم الانضمام: | edsair.doi.dedup.....82ac81bf80e6c3fd45c84e28b01e5101 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15204995 00062960 |
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