PROTEIN AGGREGATION INVITRO AND INVIVO - A QUANTITATIVE MODEL OF THE KINETIC COMPETITION BETWEEN FOLDING AND AGGREGATION

Kiefhaber, Thomas and Rudolph, Rainer and Kohler, Hans-Helmut and Buchner, Johannes (1991) PROTEIN AGGREGATION INVITRO AND INVIVO - A QUANTITATIVE MODEL OF THE KINETIC COMPETITION BETWEEN FOLDING AND AGGREGATION. BIO-TECHNOLOGY, 9 (9). pp. 825-829. ISSN 0733-222X

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Abstract

Protein aggregation is frequently observed as a major side-reaction of protein folding. We present quantitative models explaining the formation of aggregates during protein folding in vitro and in vivo on the basis of a kinetic competition between correct folding and aggregation reactions. Both models are in good agreement with experimental data. The model implies that, in vitro, the yield of native protein obtained upon refolding is determined by the rates of the competing first order folding and second order aggregation reactions. Therefore, at high protein concentrations aggregation dominates over folding and leads to the formation of insoluble protein. For in vivo protein synthesis, the model shows that the yield of native protein is only dependent on the rate of folding, on the rate of aggregation and on the rate of protein synthesis. In the cell, several mechanisms, including ''folding helpers'' seem to have evolved, which influence these processes and thereby prevent unproductive side reactions.

Item Type: Article
Uncontrolled Keywords: RIBULOSE BISPHOSPHATE CARBOXYLASE; SOLUBLE RECOMBINANT PROTEINS; ESCHERICHIA-COLI; HEAT-SHOCK; MECHANISM; GROWTH; RIBONUCLEASE-T1; RECONSTITUTION; DEHYDROGENASE; PURIFICATION
Subjects: 500 Science > 540 Chemistry & allied sciences
500 Science > 570 Life sciences
Divisions: Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie
Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie > Chair of Physical Chemistry I
Depositing User: Petra Gürster
Date Deposited: 06 Sep 2024 06:53
Last Modified: 06 Sep 2024 06:53
URI: https://pred.uni-regensburg.de/id/eprint/54876

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