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To Boil an Egg: Substrate Binding Affects Critical Stability in Thermal Unfolding of Proteins

DOI: 10.1021/acs.jpcb.7b10643 DOI Help

Authors: Rohanah Hussain (Diamond Light Source) , Charlotte S. Hughes (Diamond Light Source) , Tamas Javorfi (Diamond Light Source) , Giuliano Siligardi (Diamond Light Source) , Paul Williams (University of Nottingham) , Boyan B. Bonev (University of Nottingham)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: The Journal Of Physical Chemistry B

State: Published (Approved)
Published: February 2018
Diamond Proposal Number(s): 15146 , 13634 , 12545 , 12923

Abstract: Thermal unfolding of proteins is used extensively in screening of drug candidates because molecular interactions with ligands and substrates affect strongly protein stability, transition temperature and cooperativity. We use synchrotron radiation circular dichroism to monitor the thermal evolution of secondary structure in proteins as they approach the melting point and the impact of substrate on their thermal behaviour. Using Landau free energy expansion, we quantify transition strength and proximity to a critical point through the relative separation τ+ between the transition temperature Tm and the spinodal T+, obtained from the equation of state. The weakest transition was observed in lysozyme with τ+=0.0167 followed by holo albumin with τ+=0.0208 with a strongest transition in monomeric apo albumin τ+=0.0242. A structural transition at 45°C in apo albumin leads to a non-cooperative melt with τ+=0.00532 and amyloidogenic increase in beta content.

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Instruments: B23-Circular Dichroism