L-Arginine hydrochloride increases the solubility of folded and unfolded recombinant plasminogen activator rPA.
Summary of "L-Arginine hydrochloride increases the solubility of folded and unfolded recombinant plasminogen activator rPA."
L-Arginine hydrochloride (L-ArgHCl) was found to be an effective enhancer for in vitro protein refolding more than two decades ago. A detailed understanding of the mechanism of action, by which L-ArgHCl as co-solvent is capable to effectively suppress protein aggregation, while protein stability is preserved, has remained elusive. Concepts for the effects of co-solvents, which have been established over the last decades, were found to be insufficient to completely explain the effects of L-ArgHCl on protein refolding.In this paper we present data, which clearly establish that L-ArgHCl acts on the equilibrium solubility of the native model protein rPA, while for S-carboxymethylated rPA (IAA-rPA) that served as a model protein for denatured protein states, equilibrium solubilities could not be obtained. Solid to solute free transfer energies for native rPA were lowered by up to 14 kJ mol(-1) under the tested conditions. This finding is in marked contrast to a previously proposed model in which L-ArgHCl acts as a neutral crowder which exclusively has an influence on the stability of the transition state of aggregation. The effects on the apparent solubility of IAA-rPA as well as on the aggregation kinetics of all studied protein species that were observed in the present work could tentatively explained within the framework of a nucleation-aggregation scheme, in which L-ArgHCl exerts a strong effect on the pre-equilibria leading to formation of the aggregation seed.
Institut für Biochemie und Biotechnologie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany.
This article was published in the following journal.
Name: Protein science : a publication of the Protein Society
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Medical and Biotech [MESH] Definitions
A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES.
A cellular response to environmental insults that cause disruptions in PROTEIN FOLDING and/or accumulation of defectively folded protein in the ENDOPLASMIC RETICULUM. It consists of a group of regulatory cascades that are triggered as a response to altered levels of calcium and/or the redox state of the endoplasmic reticulum. Persistent activation of the unfolded protein response leads to the induction of APOPTOSIS.
Conformational transitions of a protein from unfolded states to a more folded state.
Important modulators of the activity of plasminogen activators. Four inhibitors, all belonging to the serpin family of proteins, have been implicated in plasminogen activation inhibition. They are PAI-1; PAI-2; protease-nexin; and PROTEIN C INHIBITOR; (PAI-3). All inhibit both the tissue-type and urokinase-type plasminogen activators.
An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN.