Study on effect of electrostatic interactions on stability of electron transfer complexes and amyloid fibrils

2014 Fiscal Year Final Research Report

• Project/Area Number: 25870407
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry; Biophysics
• Research Institution: Osaka University
• Principal Investigator: LEE Young-Ho 大阪大学, たんぱく質研究所, 講師 (70589431)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: Amyloid fibril / Binding thermodynamics / Calorimetry / Electron transfer / Electrostatics / Enzyme activity / Interprotein interaction / Protein misfolding

Outline of Final Research Achievements

We have conducted thermodynamic studies on binding reactions between ferredoxin (Fd) and sulfite reductase (SiR) as well as Fd and ferredoxin NADP(+)-reductase (FNR) using calorimetry, NMR spectroscopy, and X-ray crystallographic analysis with FNR and SiR activity assays.
We have revealed that oppositely-charged Fd and SiR formed the electron transfer complex using attractive charge-charge interactions, and that non-electrostatic interactions was also important for fine tuning of binding modes between Fd and SiR to optimize SiR activity. The same results were also obtained in the binding system between Fd and FNR. We have also revealed that amyloid fibrils of alpha-synuclein cold-denatured below 293K due to the repulsive electrostatic interactions at low temperature.
We have clearly demonstrated that interprotein electrostatic interactions play an important roles in normal protein functions and in clearance of disease-related amyloid fibrils.

Free Research Field

蛋白質科学