Role of native-state topology in the stabilization of intracellular antibodies

Biophysical Journal
Giovanni SettanniAmos Maritan

Abstract

The role played by the geometric position of each amino acid in the folding process of the immunoglobulin (Ig) variable domain is identified and measured through molecular dynamics simulations of models based on the topology of its native state. This measure allows identifying the parts of the protein that, for geometrical reasons, when mutated, would result in relevant protein stability changes. Simulations were performed without considering the covalent disulfide bond present in most of the Ig domains. The results are in good agreement with site-directed mutagenesis experiments on the folding of intracellular antibodies in which the disulfide bond does not form. We also found agreement with data on amino acid conservation in the Ig variable domain sequences. This indicates a new way for a rational approach to the design of intracellular antibodies more resistant to the suppression of the disulfide bond that occurs in the cytoplasm.

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Citations

Apr 29, 2009·International Journal of Molecular Sciences·Ronald D Hills, Charles L Brooks
Jul 27, 2002·Protein Science : a Publication of the Protein Society·Cristian MichelettiAmos Maritan
Apr 14, 2005·Proteins·Stefano PianaUrsula Rothlisberger
Dec 24, 2002·Biophysical Journal·Giovanni SettanniAmos Maritan

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