Kinetics of protein fibril formation: Methods and mechanisms.
Amyloid fibril formation is a self-assembly reaction induced by favourable conformational changes of proteins leading to a stable, structurally organized aggregates. The deposition of stable protein fibrils in organs and tissues results in many diseases which are generally referred as amyloidosis. Though different disease conditions originate from sequentially and structurally different proteins, their fibrillar forms share common structural features. In vitro, fibril structure and kinetic pathway are investigated by using spectroscopic (fluorescence, circular dichroism, crystallography and solid state-NMR) and microscopic techniques. The kinetics of fibril formation is analysed using different mechanisms to understand the microscopic processes involved in the fibrillation reaction. This review discusses the assumptions, mechanisms, and limitations of some of the widely applied kinetic equations. Understanding of these equations would help to quantify the effect of the different microscopic process on the overall fibrillation kinetics which could aid in designing appropriate molecules to intervene in the aggregation process at different stages.
Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.
E Kiran
EK
Kumar
Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India.
Neshatul
N
Haque
Department of Biotechnology and Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India. Electronic address: nppsl@uohyd.ernet.in.
N Prakash
NP
Prabhu
D000682:Amyloid / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009154:Mutation; D066329:Protein Aggregates; D011487:Protein Conformation
D000682:Amyloid; D066329:Protein Aggregates
Amyloid fibril; Elongation; Kinetic rates; Nucleation; Probes