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REVIEW: What Ultrastable Globular Proteins Teach Us about Protein Stabilization

R. Jaenicke

Institut für Biophysik und Physikalische Biochemie, Universität Regensburg, Universitätsstraße 31, D-93040 Regensburg, Germany; fax: +49 (0) 941-943-2813; E-mail: jaenicke@biologie.uni-regensburg.de

Received June 28, 1997
Proteins, due to their delicate balance of stabilizing and destabilizing interactions, are only marginally stable if physiological conditions are considered as the standard state. Enhanced intrinsic stability of "ultrastable" proteins, e.g., from extremophiles, requires only minute local structural changes. Thus, general strategies of stabilization are not available for temperature, pH, salt, or pressure adaptation. Mechanisms of enhanced thermal stability involve improved packing or docking of structural elements (domains, subunits), as well as specific local interactions, e.g., networks of ion pairs. Relating the structure and stability of eye lens crystallins (which do not undergo any turnover during the life time of an organism), point mutations, nicking and swapping of domains, grafting of linker peptides between domains, and denaturation-renaturation allowed the cumulative nature of protein stability and its relation to the hierarchy of protein structure and folding to be established. In this review, recent results for crystallins and enzymes from hyperthermophiles will be discussed as models to illustrate mechanisms of protein stabilization.
KEY WORDS: association, chaperons, crystallins, domains, extremophiles, eye lens proteins, folding, fragments, glycolytic enzymes, linker peptide, oligomeric proteins, self-assembly, stabilization, thermophilia