Inhibition of amyloid fibril formation in the variable domain of λ6 light chain mutant Wil caused by the interaction between its unfolded state and epigallocatechin-3-O-gallate

Yoshito Abe, Naoki Odawara, Nantanat Aeimhirunkailas, Hinako Shibata, Naoki Fujisaki, Hirofumi Tachibana, Tadashi Ueda

研究成果: Contribution to journalArticle査読

3 被引用数 (Scopus)

抄録

Background: Light chains are abnormally overexpressed from disordered monoclonal B-cells and form amyloid fibrils, which are then deposited on the affected organ, leading to a form of systemic amyloidosis known as AL (Amyloid Light chain) amyloidosis. A green tea catechin, epigallocatechin-3-O-gallate (EGCG), which is thought to inhibit various amyloidoses, is a potent inhibitor of amyloid fibril formation in AL amyloidosis. Methods: An amyloidogenic variable domain in λ6 light chain mutant, Wil was incubated in the presence of EGCG. The incubation products were analyzed by SDS-PAGE and reverse-phase HPLC. The interaction between Wil and EGCG was observed by using NMR and tryptophan fluorescence. Results: EGCG inhibited the amyloid fibril formation of Wil at pH 7.5 and 42 °C. Under these conditions, most Wil populations were in the unfolded state and several chemical reactions, i.e., oxidation and/or covalent bond oligomerization could be induced by auto-oxidated EGCG. Moreover, we found that EGCG bound to the unfolded state of Wil with higher affinity (Kd = 7 μM). Conclusions: Inhibition of amyloid fibril formation of Wil was caused by 1) EGCG binding to unfolded state rather than folded state and 2) chemical modifications of Wil by auto oxidation of EGCG. General significance: In the competitive formation of amyloid fibrils and off-pathway oligomers, EGCG produces the latter immediately after it preferentially binds to the unfolded state. It may be general mechanism of EGCG inhibition for amyloidosis.

本文言語英語
ページ(範囲)2570-2578
ページ数9
ジャーナルBiochimica et Biophysica Acta - General Subjects
1862
12
DOI
出版ステータス出版済み - 12 2018

All Science Journal Classification (ASJC) codes

  • 生物理学
  • 生化学
  • 分子生物学

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