期刊
BIOCHEMISTRY
卷 57, 期 37, 页码 5415-5426出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.biochem.8b00619
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资金
- JSPS KAKENHI [15H04362, 15K14458, 17K15074]
- MEXT KAKENHI [16H00836, 17H06352]
- SENTAN from the Japan Agency for Medical Research and development (AMED)
- Grants-in-Aid for Scientific Research [15H04362, 15K14458, 16H00836, 17K15074] Funding Source: KAKEN
Although ovalbumin (OVA), a main component of hen egg white and a non-inhibitory serpin superfamily protein, has been reported to form fibrilar aggregates, its relationship with amyloid fibrils associated with various degenerative diseases is unclear. We studied the heat-induced aggregation of intact OVA using an amyloid-specific thioflavin T assay with a fluorometer or direct imaging with a light emitting diode lamp and several physicochemical approaches, and the results confirmed that intact OVA forms aggregates with a small part of amyloid cores and dominantly amorphous aggregates. We isolated the amyloidogenic core peptide by proteolysis with trypsin. The isolated 23-residue peptide, pOVA, with marked amyloidogenicity, corresponded to one (beta-strand 3A) of the key regions involved in serpin latency transition and domain-swap polymerization leading to serpinopathies. Although the strong amyloidogenicity of pOVA was suppressed in a mixture of tryptic digests, it was observed under acidic conditions in the presence of various salts, with which pOVA has a positive charge. Cytotoxicity measurements suggested that, although heat-treated OVA aggregates exhibited the strongest toxicity, it was attributed to a general property of amorphous aggregates rather than amyloid toxicity. Predictions indicated that the high amyloidogenicity of the beta-strand 3A region is common to various serpins. This suggests that the high amyloidogenicity of beta-strand 3A that is important for serpin latency transition and domain-swap polymerization is retained in OVA and constitutes beta-spine amyloid cores upon heat aggregation.
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