Aggregation of the amyloid β (Aβ) peptide into fibrils represents one of the major biochemical pathways underlying the development of Alzheimer's disease (AD). Extensive studies have been carried out to understand the role of fibrillar seeds on the overall kinetics of amyloid aggregation. However, the precise effect of seeds that are structurally or sequentially different from Aβ on the structure of the resulting amyloid aggregates is yet to be fully understood. In this work, we use nanoscale infrared spectroscopy to probe the spectral facets of individual aggregates formed by aggregating Aβ42 with antiparallel fibrillar seeds of Aβ (16-22) and E22Q Aβ (1-40) Dutch mutant and demonstrate that Aβ can form heterotypic or mixed polymorphs that deviate significantly from its expected parallel cross β structure. We further show that formation of heterotypic aggregates is not limited to coaggregation of Aβ and its isomers, and that the former can form heterotypic fibrils with alpha synuclein and brain protein lysates. These findings highlight the complexity of Aβ aggregation in AD and underscore the need to explore how Aβ interacts with other brain components, which is crucial for developing better therapeutic strategies for AD.
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http://dx.doi.org/10.1101/2024.03.15.585264 | DOI Listing |
J Biol Chem
February 2023
Department of Structural Biology, Van Andel Institute, Grand Rapids, Michigan, USA. Electronic address:
The Saccharomyces cerevisiae Yta7 is a chromatin remodeler harboring a histone-interacting bromodomain (BRD) and two AAA+ modules. It is not well understood how Yta7 recognizes the histone H3 tail to promote nucleosome disassembly for DNA replication or RNA transcription. By cryo-EM analysis, here we show that Yta7 assembles a three-tiered hexamer with a top BRD tier, a middle AAA1 tier, and a bottom AAA2 tier.
View Article and Find Full Text PDFJ Environ Manage
February 2022
Department of Civil Engineering, Lassonde School of Engineering, York University, ON, M3J1P3, Canada. Electronic address:
The interest in the A-stage of the adsorption/bio-oxidation (A/B) process has considerably increased due to its capacity of carbon redirection to the solids stream. Induced by its flexible and compact design, the Alternating Activated Adsorption (AAA) was recently implemented in full-scale as an alternative A-stage system. However, the literature on such a system is scarce.
View Article and Find Full Text PDFCell Rep
June 2019
Department of Crystallography, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London WC1E 7HX, UK. Electronic address:
AAA+ proteins form asymmetric hexameric rings that hydrolyze ATP and thread substrate proteins through a central channel via mobile substrate-binding pore loops. Understanding how ATPase and threading activities are regulated and intertwined is key to understanding the AAA+ protein mechanism. We studied the disaggregase ClpB, which contains tandem ATPase domains (AAA1, AAA2) and shifts between low and high ATPase and threading activities.
View Article and Find Full Text PDFElife
November 2018
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, France.
The biogenesis of 60S ribosomal subunits is initiated in the nucleus where rRNAs and proteins form pre-60S particles. These pre-60S particles mature by transiently interacting with various assembly factors. The ~5000 amino-acid AAA+ ATPase Rea1 (or Midasin) generates force to mechanically remove assembly factors from pre-60S particles, which promotes their export to the cytosol.
View Article and Find Full Text PDFJ Biol Chem
December 2018
From the Department of Biology, Faculty of Science and Engineering and
ClpB, a bacterial homologue of heat shock protein 104 (Hsp104), can disentangle aggregated proteins with the help of the DnaK, a bacterial Hsp70, and its co-factors. As a member of the expanded superfamily of ATPases associated with diverse cellular activities (AAA), ClpB forms a hexameric ring structure, with each protomer containing two AAA modules, AAA1 and AAA2. A long coiled-coil middle domain (MD) is present in the C-terminal region of the AAA1 and surrounds the main body of the ring.
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