The Effect of Alcohol on beta2-Microglobulin Amyloid Fibrils

Hirota-Nakaoka, Nami; Hasegawa, Kyohei; Naiki, H.; Goto, Yoshiro

doi:10.2142/biophys.41.s169_4

Cited by 19 publications

(28 citation statements)

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“…The extensive hydrogen bond network of the β‐structure, more than that of the native globular state, is likely to confer rigidity on the amyloid fibrils and resistance to protease digestion. The observation that amyloid fibrils were completely dissolved by dimethylsulfoxide also supports the importance of hydrogen bonds in the stability of amyloid fibrils [40]. In addition, the depolymerization of the amyloid fibrils at neutral pH regions is consistent with an idea that intricate network of electrostatic interactions including the hydrogen bonds and salt bridges is important.…”

Section: Discussionsupporting

confidence: 71%

Conformational stability of amyloid fibrils of β₂‐microglobulin probed by guanidine‐hydrochloride‐induced unfolding

et al. 2004

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Although the stability of globular proteins has been studied extensively, that of amyloid fibrils is scarcely characterized. Beta2-microglobulin (beta2-m) is a major component of the amyloid fibrils observed in patients with dialysis-related amyloidosis. We studied the effects of guanidine hydrochloride on the amyloid fibrils of beta2-m, revealing a cooperative unfolding transition similar to that of the native state. The stability of amyloid fibrils increased on the addition of ammonium sulfate, consistent with a role of hydrophobic interactions. The results indicate that the analysis of unfolding transition is useful to obtain insight into the structural stability of amyloid fibrils.

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Section: Discussionsupporting

confidence: 71%

Conformational stability of amyloid fibrils of β₂‐microglobulin probed by guanidine‐hydrochloride‐induced unfolding

et al. 2004

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“…Purified and lyophilized K3 peptide was difficult to completely dissolve in water under acidic pH conditions, exhibiting turbidity and a high background as monitored by ThT fluorescence. Among the various solvent conditions examined, we found that a high concentration of Me 2 SO, which was also useful for dissolving ␤ 2 m amyloid fibrils (31,44), could completely dissolve the K3 peptide. Therefore, we used 100% Me 2 SO to prepare a stock solution of the K3 peptide, which was mostly used within the same day.…”

Section: Resultsmentioning

confidence: 99%

Optimum Amyloid Fibril Formation of a Peptide Fragment Suggests the Amyloidogenic Preference of β2-Microglobulin under Physiological Conditions

Ohhashi

Hara

Naiki

et al. 2004

Journal of Biological Chemistry

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␤ 2 -Microglobulin (␤ 2 m) is a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. Although full-length ␤ 2 m readily forms amyloid fibrils in vitro by seed-dependent extension with a maximum at pH 2.5, fibril formation under physiological conditions as detected in patients has been difficult to reproduce. A 22-residue K3 peptide of ␤ 2 m, Ser 20 -Lys 41 , obtained by digestion with Acromobacter protease I, forms amyloid fibrils without seeding. To obtain further insight into the mechanism of fibril formation, we studied the pH dependence of fibril formation of the K3 peptide and its morphology using a ThT fluorescence assay and electron microscopy, respectively. K3 peptide formed amyloid fibrils over a wide range of pH values with an optimum around pH 7 and contrasted with the pH profile of the seed-dependent extension reaction of full-length ␤ 2 m. This suggests that once the rigid native-fold of ␤ 2 m is unfolded and additional factors triggering the nucleation process are provided, full-length ␤ 2 m discloses an intrinsic potential to form amyloid fibrils at neutral pH. The fibril formation was strongly promoted by dimerization of K3 through Cys 25 . The morphology of the fibrils varied depending on the fibril formation conditions and the presence or absence of a disulfide bond. Various fibrils had the potential to seed fibril formation of full-length ␤ 2 m accompanied with a characteristic lag phase, suggesting that the internal structures are similar.Amyloid fibrils are recognized as being associated with the pathology of more than 20 serious human diseases and the responsible peptides or proteins specific to these diseases have been identified (1-5). These fibrils are characterized by a cross-␤ structure where ␤-strands are perpendicularly oriented to the axis of the polymeric fibril (6 -8). Moreover, various proteins and peptides that are not related to diseases can also form amyloid-like fibers, implying that formation of amyloid fibrils is a general property of polypeptides (7, 9 -14). Clarifying the mechanism of amyloid fibril formation is essential not only for understanding the pathogenesis of amyloidosis but also for improving our understanding of the mechanism of protein folding.Dialysis-related amyloidosis is a common and serious complication among patients on long term hemodialysis (15, 16), in which ␤ 2 -microglobulin (␤ 2 m) 1 forms amyloid fibrils. Native ␤ 2 m, made of 99 amino acid residues, corresponds to a typical immunoglobulin domain ( Fig. 1) and is a component of the type I major histocompatibility antigen (17)(18)(19). Although the increase in ␤ 2 m concentration in blood over a long period is the most critical risk factor causing amyloidosis, the molecular details remain unknown. Recently ␤ 2 m, because of its relatively small size, which makes it suitable for physicochemical studies, has been used as a target for extensive studies addressing the mechanism of amyloid fibril formation in the context of protein conformation (20 -28). We have st...

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“…It has been postulated that the generic amyloid conformation, the cross-␤ structure (2), may be a universal, energetic minimum for aggregated proteins (3,4). Once formed, amyloid fibrils are extremely stable and difficult to solubilize (5).…”

mentioning

confidence: 99%

Molecular basis for amyloid fibril formation and stability

Makin

Atkins²,

Sikorski³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

625

586

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The molecular structure of the amyloid fibril has remained elusive because of the difficulty of growing well diffracting crystals. By using a sequence-designed polypeptide, we have produced crystals of an amyloid fiber. These crystals diffract to high resolution (1 Å) by electron and x-ray diffraction, enabling us to determine a detailed structure for amyloid. The structure reveals that the polypeptides form fibrous crystals composed of antiparallel ␤-sheets in a cross-␤ arrangement, characteristic of all amyloid fibers, and allows us to determine the side-chain packing within an amyloid fiber. The antiparallel ␤-sheets are zipped together by means of -bonding between adjacent phenylalanine rings and salt-bridges between charge pairs (glutamic acid-lysine), thus controlling and stabilizing the structure. These interactions are likely to be important in the formation and stability of other amyloid fibrils.x-ray diffraction ͉ side-chain packing ͉ structure ͉ -bonding ͉ ␤-sheet interaction

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The Effect of Alcohol on beta2-Microglobulin Amyloid Fibrils

Cited by 19 publications

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Conformational stability of amyloid fibrils of β₂‐microglobulin probed by guanidine‐hydrochloride‐induced unfolding

Conformational stability of amyloid fibrils of β₂‐microglobulin probed by guanidine‐hydrochloride‐induced unfolding

Optimum Amyloid Fibril Formation of a Peptide Fragment Suggests the Amyloidogenic Preference of β2-Microglobulin under Physiological Conditions

Molecular basis for amyloid fibril formation and stability

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The Effect of Alcohol on beta2-Microglobulin Amyloid Fibrils

Cited by 19 publications

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Conformational stability of amyloid fibrils of β2‐microglobulin probed by guanidine‐hydrochloride‐induced unfolding

Conformational stability of amyloid fibrils of β2‐microglobulin probed by guanidine‐hydrochloride‐induced unfolding

Optimum Amyloid Fibril Formation of a Peptide Fragment Suggests the Amyloidogenic Preference of β2-Microglobulin under Physiological Conditions

Molecular basis for amyloid fibril formation and stability

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Conformational stability of amyloid fibrils of β₂‐microglobulin probed by guanidine‐hydrochloride‐induced unfolding

Conformational stability of amyloid fibrils of β₂‐microglobulin probed by guanidine‐hydrochloride‐induced unfolding