Steric Zipper of the Amyloid Fibrils Formed by Residues 109–122 of the Syrian Hamster Prion Protein

Lee, Shin-Wen; Mou, Yun; Lin, Shu‐Yi; Chou, Fang‐Chieh; Tseng, W. F.; Chen, Chun‐hsien; Lu, Chun‐Yi; Yu, Steve S.‐F.; Chan, Jerry C. C.

doi:10.1016/j.jmb.2008.03.035

Cited by 55 publications

(58 citation statements)

References 91 publications

(85 reference statements)

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“…It is comprised of a cross β-sheet structure in which the polypeptide chain is arranged in β-sheets stacked perpendicular to the axis of the fibril forming a steric zipper [52][53][54][55][56]. Amyloid fibrils are composed of two to six protofibrils that plait together to form rope-like structures of 5 to 10 nm in diameter and up to hundreds of nm in length.…”

Section: Shsps and Diseasementioning

confidence: 99%

“…the typical cross β-sheet array formed from sheets of β-strands lying perpendicular to the axis of the fibril and the aligning of these β-sheets into individual filaments (from [52]). (C and D) Structural models of amino acids that compromise the steric zipper that forms the core of fibrils from (C) the peptide GNNQQNY [53] and (D) residues 109-122 of the Syrian hamster prion protein [56]. The arrows indicate the direction of the fibril axis.…”

Section: Crystallin Proteins As Bionanomaterialsmentioning

confidence: 99%

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Crystallin proteins and amyloid fibrils

Ecroyd

Carver

2008

Cell. Mol. Life Sci.

221

234

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Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. The major lens protein, alpha-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer's and Parkinson's). In this review, the literature on the interaction of alpha B-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, the ability of sHsps to prevent fibril formation, their mechanisms of action and the possible in vivo consequences of such associations are discussed. Finally, the fibril-forming propensity of the crystallin proteins and its implications for cataract formation are described along with the potential use of fibrillar crystallin proteins as bionanomaterials. Improper protein folding (misfolding) can lead to the formation of disordered (amorphous) or ordered (amyloid fibril) aggregates. The major lens protein, α-crystallin, is a member of the small heat-shock protein (sHsp) family of intracellular molecular chaperone proteins that prevent protein aggregation. Whilst the chaperone activity of sHsps against amorphously aggregating proteins has been well studied, its action against fibril-forming proteins has received less attention despite the presence of sHsps in deposits found in fibril-associated diseases (e.g. Alzheimer's and Parkinson's). In this review, the literature on the interaction of αB-crystallin and other sHsps with fibril-forming proteins is summarized. In particular, the ability of sHsps to prevent fibril formation, their mechanisms of action and the possible in vivo consequences of such associations are discussed. Finally, the fibril-forming propensity of the crystallin proteins and its implications for cataract formation are described along with the potential use of fibrillar crystallin proteins as bionanomaterials.

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Section: Shsps and Diseasementioning

confidence: 99%

Section: Crystallin Proteins As Bionanomaterialsmentioning

confidence: 99%

Crystallin proteins and amyloid fibrils

Ecroyd

Carver

2008

Cell. Mol. Life Sci.

221

234

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“…30 Experimental evidence has been consistent with the theoretical models of some peptides. 9,26,31,32 However, there exist peptide sequences (e.g., NNFGAIL) 14,33 for which X-ray crystallography is inconsistent with a central role for a steric zipper, in that the data show little to no interdigitation between β-sheets although the overall bilayer is retained.…”

Section: ■ Introductionmentioning

confidence: 99%

Factors That Drive Peptide Assembly and Fibril Formation: Experimental and Theoretical Analysis of Sup35 NNQQNY Mutants

Thanh¹,

Economou²,

LaPointe³

et al. 2013

J. Phys. Chem. B

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Residue mutations have substantial effects on aggregation kinetics and propensities of amyloid peptides and their aggregate morphologies. Such effects are attributed to conformational transitions accessed by various types of oligomers such as steric zipper or single β-sheet. We have studied the aggregation propensities of six NNQQNY mutants: NVVVVY, NNVVNV, NNVVNY, VIQVVY, NVVQIY, and NVQVVY in water using a combination of ion-mobility mass spectrometry, transmission electron microscopy, atomic force microscopy, and all-atom molecular dynamics simulations. Our data show a strong correlation between the tendency to form early β-sheet oligomers and the subsequent aggregation propensity. Our molecular dynamics simulations indicate that the stability of a steric zipper structure can enhance the propensity for fibril formation. Such stability can be attained by either hydrophobic interactions in the mutant peptide or polar side-chain interdigitations in the wild-type peptide. The overall results display only modest agreement with the aggregation propensity prediction methods such as PASTA, Zyggregator, and RosettaProfile, suggesting the need for better parametrization and model peptides for these algorithms.

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“…3). Furthermore, the three-dimensional structures of some prion protein fragments have also been determined, which could be transformed into amyloid fibrils [41]. The small peptide of human PrP (residues 106-126), which is partially resistant to proteinase K, presents a high b-sheet-enriched structure, and forms amyloid fibrils in vitro [42,43].…”

Section: Prpmentioning

confidence: 99%

Prion protein oligomer and its neurotoxicity

Huang

Lian

Wen

et al. 2013

ABBS

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The prion diseases, also known as transmissible spongiform encephalopathies, are fatal neurodegenerative disorders. According to the 'protein only' hypothesis, the key molecular event in the pathogenesis of prion disease is the conformational conversion of the host-derived cellular prion protein (PrP C ) into a misfolded form (scrapie PrP, PrP Sc ). Increasing evidence has shown that the most infectious factor is the smaller subfibrillar oligomers formed by prion proteins. Both the prion oligomer and PrP Sc are rich in b-sheet structure and resistant to the proteolysis of proteinase K. The prion oligomer is soluble in physiologic environments whereas PrP Sc is insoluble. Various prion oligomers are formed in different conditions. Prion oligomers exhibited more neurotoxicity both in vitro and in vivo than the fibrillar forms of PrP Sc , implying that prion oligomers could be potential drug targets for attacking prion diseases. In this article, we describe recent experimental evidence regarding prion oligomers, with a special focus on prion oligomer formation and its neurotoxicity.

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Steric Zipper of the Amyloid Fibrils Formed by Residues 109–122 of the Syrian Hamster Prion Protein

Cited by 55 publications

References 91 publications

Crystallin proteins and amyloid fibrils

Crystallin proteins and amyloid fibrils

Factors That Drive Peptide Assembly and Fibril Formation: Experimental and Theoretical Analysis of Sup35 NNQQNY Mutants

Prion protein oligomer and its neurotoxicity

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