Cooperative unfolding of apolipoprotein A-1 induced by chemical denaturation.

Autor: Eckhardt D; Universität Freiburg, Institut für Pharmazeutische Wissenschaften, Hermann-Herder Str. 9, D-79104 Freiburg, Germany., Li-Blatter X; University of Basel, Biozentrum, Klingelbergstrasse 70, CH-4056 Basel, Switzerland., Schönfeld HJ; Schönfeld-Protein Science Consulting, Marienmattenweg 7, D-79115 Freiburg, Germany., Heerklotz H; Universität Freiburg, Institut für Pharmazeutische Wissenschaften, Hermann-Herder Str. 9, D-79104 Freiburg, Germany., Seelig J; University of Basel, Biozentrum, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Electronic address: joachim.seelig@unibas.ch.
Jazyk: angličtina
Zdroj: Biophysical chemistry [Biophys Chem] 2018 Sep; Vol. 240, pp. 42-49. Date of Electronic Publication: 2018 May 25.
DOI: 10.1016/j.bpc.2018.05.005
Abstrakt: Apolipoprotein A-1 (Apo A-1) plays an important role in lipid transfer and obesity. Chemical unfolding of α-helical Apo A-1 is induced with guanidineHCl and monitored with differential scanning calorimetry (DSC) and CD spectroscopy. The unfolding enthalpy and the midpoint temperature of unfolding decrease linearly with increasing guanidineHCl concentration, caused by the weak binding of denaturant. At room temperature, binding of 50-60 molecules guanidineHCl leads to a complete Apo A-1 unfolding. The entropy of unfolding decreases to a lesser extent than the unfolding enthalpy. Apo A-1 chemical unfolding is a dynamic multi-state equilibrium that is analysed with the Zimm-Bragg theory modified for chemical unfolding. The chemical Zimm-Bragg theory predicts the denaturant binding constant K D and the protein cooperativity σ. Chemical unfolding of Apo A-1 is two orders of magnitude less cooperative than thermal unfolding. The free energy of thermal unfolding is ~0.2 kcal/mol per amino acid residue and ~1.0 kcal/mol for chemical unfolding at room temperature. The Zimm-Bragg theory calculates conformational probabilities and the chemical Zimm-Bragg theory predicts stretches of α-helical segments in dynamic equilibrium, unfolding and refolding independently and fast.
(Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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