14 research outputs found
Kinetics of Amyloid Formation by Different Proteins and Peptides: Polymorphism and Sizes of Folding Nuclei of Fibrils
Aggregation of peptides and proteins into amyloid structure is one of the most intensively studied biological phenomena at the moment. To date, there is no developed theory that would allow one to determine what kind of mechanism presents in the given experiment on the basis of aggregation kinetic data. Debates concerning the mechanism of the amyloid fibrils formation and, in particular, the size of the amyloidogenic nucleus are still going on. We created such a theory on the basis of the kinetics of amyloid aggregates formation. In the presented chapter, theoretical and experimental approaches were employed for studding the process of amyloid formation by different proteins and peptides. The current kinetic models described in this chapter adequately describe the key features of amyloid nucleation and growth
What is Responsible for Atypical Dependence of the Rate of Amyloid Formation on Protein Concentration: Fibril-Catalyzed Initiation of New Fibrils or Competition with Oligomers?
An abnormal dependence of the rate
of amyloid formation on protein
concentration has been recently observed by Meisl et al. for Aβ40
peptides associated with Alzheimer’s disease. To explain this
effect, Meisl et al. proposed a novel mechanism of fibril growth:
the fibril-catalyzed initiation of fibril formation. In this paper
we offer an alternative explanation of the observed anomalous kinetics:
formation of metastable oligomers competing with fibril formation
by decreasing the concentration of the fibril-forming free monomers.
Here we show that the oligomer sizes resulting from the anomalous
dependence of the fibril growth rate on protein concentration are
close to the sizes of oligomers observed by electron microscopy
How to Determine the Size of Folding Nuclei of Protofibrils from the Concentration Dependence of the Rate and Lag-Time of Aggregation. I. Modeling the Amyloid Protofibril Formation
The question about the size of nuclei
of formation of protofibrils
(which constitute mature amyloid fibrils) formed by different proteins
and peptides is yet open and debatable because of the absence of solid
knowledge of underlying mechanisms of amyloid formation. In this work,
a kinetic model of the process of formation of amyloid protofibrils
is suggested, which allows calculation of the size of the nuclei using
only kinetic data. In addition to the stage of primary nucleation,
which is believed to be present in many protein aggregation processes,
the given model includes both linear growth of protofibrils (proceeding
only at the cost of attaching of monomers to the ends) and exponential
growth of protofibrils at the cost of growth from the surface, branching,
and fragmentation with the secondary nuclei. Theoretically, only the
exponential growth is compatible with the existence of a pronounced
lag-period (which can take much more time then the growth of aggregates
themselves). The obtained analytical solution allows us to determine
the size of the primary and secondary nuclei from the experimentally
obtained concentration dependences of the time of growth and the new
parameterthe ratio <i>L</i><sub>rel</sub> of the
lag-time duration to the time of growth of amyloid protofibrils
Knomics-Biota - a system for exploratory analysis of human gut microbiota data
Abstract Background Metagenomic surveys of human microbiota are becoming increasingly widespread in academic research as well as in food and pharmaceutical industries and clinical context. Intuitive tools for investigating experimental data are of high interest to researchers. Results Knomics-Biota is a web-based resource for exploratory analysis of human gut metagenomes. Users can generate and share analytical reports corresponding to common experimental schemes (like case-control study or paired comparison). Interactive visualizations and statistical analysis are provided in association with the external factors and in the context of thousands of publicly available datasets arranged into thematic collections. The web-service is available at https://biota.knomics.ru. Conclusions Knomics-Biota web service is a comprehensive tool for interactive metagenomic data analysis