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Studying Protein Structure and Function by Directed Evolution

Examples with Engineered Antibodies

  • Chapter
Protein Dynamics, Function, and Design

Part of the book series: NATO ASI Series ((NSSA,volume 301))

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Abstract

Directed molecular evolution is a powerful strategy for investigating the structure and function of proteins. When a function, such as ligand binding, can only be carried out by the native state of the protein, the biological selection for this function can be used to improve structural properties of the protein. Thus, thermodynamic stability and folding efficiency, which is the ability to avoid aggregation during folding, can be optimized. Three methods of selection are reviewed: phage display, selectively infective phages (SIP) and ribosome display, a cell-free method. Examples for optimizing antibody stability are discussed. In one case, antibodies have been generated under evolutionary pressure, which are stable in the absence of any disulfide bond, in the other case, a kink in the first strand of the beta-sandwich of kappa domains has been optimized.

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Authors and Affiliations

  1. Biochemisches Institut, Universität Zürich, Winterthurerstr. 190, CH-8057, Zürich, Switzerland

    Andreas Plückthun

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  1. Andreas Plückthun
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Editors and Affiliations

  1. Stanford University, Stanford, California, USA

    Oleg Jardetzky  & Robin E. Holbrook  & 

  2. Université Louis Pasteur, Illkirch Graffenstaden, France

    Jean-François Lefèvre

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Plückthun, A. (1998). Studying Protein Structure and Function by Directed Evolution. In: Jardetzky, O., Lefèvre, JF., Holbrook, R.E. (eds) Protein Dynamics, Function, and Design. NATO ASI Series, vol 301. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4895-9_4

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  • DOI: https://doi.org/10.1007/978-1-4615-4895-9_4

  • Publisher Name: Springer, Boston, MA

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  • Online ISBN: 978-1-4615-4895-9

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