Unzipping the mysteries of amyloid fiber formation

Miranker, Andrew D.

doi:10.1073/pnas.0401163101

Cited by 22 publications

(13 citation statements)

References 32 publications

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“…The lag phase preceding amyloid formation is considered to reflect the low probability of multimolecular PrP interactions that result in the formation of a nucleation site suitable for the propagation of amyloid fibrils. Like crystallization, a hallmark of this process is the capacity of fiber formation to be bypassed by providing exogenous seed from a previously conducted reaction (Miranker 2004). Consequently, admixture of a small amount of pre‐formed amyloid is expected to provide suitable nucleation sites and eliminate the lag phase.…”

Section: Resultsmentioning

confidence: 99%

Rapid formation of amyloid from α‐monomeric recombinant human PrP in vitro

Tahiri-Alaoui

2005

Protein Science

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The infectious agent of prion diseases is identified with PrP Sc , a ␤-rich, amyloidogenic and partially protease resistant isoform of the cellular glycoprotein, PrP C . To understand the process of prion formation in vivo, we and others have studied defined misfolding pathways of recombinant PrP in vitro. The low-level infectivity of the in vitro misfolded murine PrP amyloid has recently been reported. Here we analyze the in vitro kinetics of amyloid formation from recombinant human PrP in vitro in the context of two common allelic forms of PrP found in human populations that are associated with differences in prion disease susceptibility and pathological phenotype. We show that human PrP amyloid forms readily from its PrP C -like state in vitro, that the lag time of the reaction can be further shortened by the presence of a "seed" of pre-formed PrP amyloid, and that amyloid propagation is more complex than a simple crystallization process. We further show that the kinetics of amyloid formation do not differ between the Met129 and Val129 allelomorphs of human PrP, and that amyloid from each functions as an equally effective seed in heterologous, as in homologous amyloid reactions. The results could illuminate the process of amyloid formation in vivo as well as help understanding prion pathogenesis.

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Section: Resultsmentioning

confidence: 99%

Rapid formation of amyloid from α‐monomeric recombinant human PrP in vitro

Tahiri-Alaoui

2005

Protein Science

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“…As a result, the analysis of the relationship between native state stability and the kinetics of amyloid Wbril formation will, for example, beneWt from the simpliWcation of structure of cc -p2 derived peptides from a trimer to a dimer. The characteristics of the cc model system are thus highly suitable for probing molecular details of the assembly of amyloid structures (Miranker, 2004). This approach has an advantage over studies of natural disease-related models, where the complexity and size of the polypeptides often hinders a systematic dissection of the driving forces of amyloid-Wbril formation.…”

Section: Discussionmentioning

confidence: 99%

De novo design of a two-stranded coiled-coil switch peptide

Kammerer

Steinmetz

2006

Journal of Structural Biology

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“…[1][2][3][4][5][6][7][8][9][10][11][12] The alternative conformations of amyloidogenic proteins and their multi-step assembly pathways have been under intense scrutiny. 11 The notion that protein aggregation is a cause, rather than an effect, of neurodegeneration has undergone numerous experimental tests.…”

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confidence: 99%