Two distinct diseases
are associated with the deposition of fibrillar
amyloid-β (Aβ) peptides in the human brain in an age-dependent
fashion. Alzheimer’s disease is primarily associated with parenchymal
plaque deposition of Aβ42, while cerebral amyloid angiopathy
(CAA) is associated with amyloid formation of predominantly Aβ40
in the cerebral vasculature. In addition, familial mutations at positions
22 and 23 of the Aβ sequence can enhance vascular deposition
in the two major subtypes of CAA. The E22Q (Dutch) mutation is associated
with CAA type 2, while the D23N (Iowa) mutation is associated with
CAA type 1. Here we investigate differences in the formation and structure
of fibrils of these mutant Aβ peptides
in vitro
to gain insights into their biochemical and physiological differences
in the brain. Using Fourier transform infrared and nuclear magnetic
resonance spectroscopy, we measure the relative propensities of Aβ40-Dutch
and Aβ40-Iowa to form antiparallel structure and compare these
propensities to those of the wild-type Aβ40 and Aβ42 isoforms.
We find that both Aβ40-Dutch and Aβ40-Iowa have strong
propensities to form antiparallel β-hairpins in the first step
of the fibrillization process. However, there is a marked difference
in the ability of these peptides to form elongated antiparallel structures.
Importantly, we find marked differences in the stability of the protofibril
or fibril states formed by the four Aβ peptides. We discuss
these differences with respect to the mechanisms of Aβ fibril
formation in CAA.
Time and again, yeast has proven to be a vital model system to understand various crucial basic biology questions. Studies related to viruses are no exception to this. This simple eukaryotic organism is an invaluable model for studying fundamental cellular processes altered in the host cell due to viral infection or expression of viral proteins. Mechanisms of infection of several RNA and relatively few DNA viruses have been studied in yeast to date. Yeast is used for studying several aspects related to the replication of a virus, such as localization of viral proteins, interaction with host proteins, cellular effects on the host, etc. The development of novel techniques based on high-throughput analysis of libraries, availability of toolboxes for genetic manipulation, and a compact genome makes yeast a good choice for such studies. In this review, we provide an overview of the studies that have used yeast as a model system and have advanced our understanding of several important viruses.
Key points• Yeast, a simple eukaryote, is an important model organism for studies related to viruses.• Several aspects of both DNA and RNA viruses of plants and animals are investigated using the yeast model.• Apart from the insights obtained on virus biology, yeast is also extensively used for antiviral development.
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