Amyloid fibril formation from a 9 amino acid peptide, 55th–63rd residues of human lysozyme

Tokunaga, Yuhei; Matsumoto, Mitsuharu; Sugimoto, Yasushi

doi:10.1016/j.ijbiomac.2015.06.015

Cited by 5 publications

(2 citation statements)

References 31 publications

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“…The hen egg-white lysozyme (HEWL) is a small protein with four disulde bonds. 39 This protein has been studied as a model of the human lysozyme, 40 whose mutation (sharing 60% of its sequence identity with HEWL) is associated with hereditary systemic amyloidosis. 41 The release of CNPs into the environment may occur as a results of common processes, such as CNPs production, CNP-containing product manufacturing, and the use and reuse of CNPs products.…”

Section: Introductionmentioning

confidence: 99%

Carbon nanospecies affecting amyloid formation

et al. 2017

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Section: Introductionmentioning

confidence: 99%

Carbon nanospecies affecting amyloid formation

et al. 2017

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“…These mutants are therefore called amyloidogenic variants. The sites of mutations in the variants converge in or near the so-called amyloidogenic core region, which is important for amyloid fibril formation 33 - 35 . Our recent study using four of the five variants revealed that, when overexpressed in cultured human embryonic kidney (HEK) 293 cells, I56T, F57I, W64R and D67H were accumulated in the ER together with GRP78/BiP while enhancing the ER stress response via the IRE1-XBP1-GRP78/BiP pathway 36 .…”

Section: Introductionmentioning

confidence: 99%

Lysozyme Mutants Accumulate in Cells while Associated at their N-terminal Alpha-domain with the Endoplasmic Reticulum Chaperone GRP78/BiP

2016

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Amyloidogenic human lysozyme variants deposit in cells and cause systemic amyloidosis. We recently observed that such lysozymes accumulate in the endoplasmic reticulum (ER) with the ER chaperone GRP78/BiP, accompanying the ER stress response. Here we investigated the region of lysozyme that is critical to its association with GRP78/BiP. In addition to the above-mentioned variants of lysozyme, we constructed lysozyme truncation or substitution mutants. These were co-expressed with GRP78/BiP (tagged with FLAG) in cultured human embryonic kidney cells, which were analyzed by western blotting and immunocytochemistry using anti-lysozyme and anti-FLAG antibodies. The amyloidogenic variants were confirmed to be strongly associated with GRP78/BiP as revealed by the co-immunoprecipitation assay, whereas N-terminal mutants pruned of 1-41 or 1-51 residues were found not to be associated with the chaperone. Single amino acid substitutions for the leucine array along the α-helices in the N-terminal region resulted in wild-type lysozyme remaining attached to GRP78/BiP. These mutations also tended to show lowered secretion ability. We conclude that the N-terminal α-helices region of the lysozyme is pivotal for its strong adhesion to GRP78/BiP. We suspect that wild-type lysozyme interacts with the GRP at this region as a step in the proper folding monitored by the ER chaperone.

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