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J. Biol. Chem., Vol. 281, Issue 31, 99925, August 4, 2006

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Mapping Multiple Mutations

Protein-protein interactions are essential for many biological processes, and they are often characterized by a striking structural plasticity that allows contact points to adapt to conformational changes and multiple amino acid substitutions. As a result, the biophysics governing protein-protein interactions is extremely complex, and an area of extensive investigation is concerned with establishing a detailed knowledge base that will enhance our understanding of protein-protein associations and enable the development of predictive criteria for engineering novel protein functions.

35 residues on the human growth hormone were used for scanning.

To aid this effort, Gábor Pál and colleagues have developed a novel combinatorial quantitative saturation scanning strategy that enables rapid assessment of the structural and functional effects of all possible mutations across a large protein-protein interface. The researchers applied their scan to the interaction between human growth hormone and its receptor. They found that the human growth hormone binding interface is highly adaptable to mutations but that the nature of the tolerated mutations challenges generally accepted views about the evolutionary and biophysical pressures governing protein-protein interactions. Many substitutions that would be considered chemically conservative are not tolerated, whereas many non-conservative substitutions are accommodated. Thus, the authors conclude that mutational tolerance is highly context-dependent and that it cannot be predicted by our current knowledge base.

FOOTNOTES

See referenced article, J. Biol. Chem. 2006, 281, 22378-22385

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This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Related Collections Papers Of The Week Social Bookmarking                      What's this?