The formation of oligomeric proteins proceeds at a major cost of reducing the translational and rotational entropy for their subunits in order to form the stabilizing interactions found in the oligomeric state. Unlike site-directed mutations, covalent linkage of subunits represents a generically applicable strategy for enhancing oligomeric stability by reducing the entropic driving force for dissociation. Although this can be realized by introducing de novo disulfide cross-links between subunits, issues with irreversible aggregation limit the utility of this approach. In contrast, tandem linkage of subunits in a single polypeptide chain offers a universal method of pre-paying the entropic cost of oligomer formation. In the present paper, thermodynamic, structural and experimental aspects of designing and characterizing tandem-linked oligomers are discussed with reference to engineering a stabilized tetramer of the oligomerization domain of the human p53 tumour-suppressor protein by tandem dimerization.
Enhancement of oligomeric stability by covalent linkage and its application to the human p53tet domain: thermodynamics and biological implications
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G.M.K. Poon; Enhancement of oligomeric stability by covalent linkage and its application to the human p53tet domain: thermodynamics and biological implications. Biochem Soc Trans 1 December 2007; 35 (6): 1574–1578. doi: https://doi.org/10.1042/BST0351574
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