Mutagenic dissection of the sequence determinants of protein folding, recognition, and machine function


  • Robert T. Sauer

    Corresponding author
    1. Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts
    • Correspondence to: Robert T. Sauer, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139. E-mail:

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    • Robert Sauer is the recipient of the Protein Society 2013 Stein & Moore Award.


Understanding the relationship between the amino-acid sequence of a protein and its ability to fold and to function is one of the major challenges of protein science. Here, cases are reviewed in which mutagenesis, biochemistry, structure determination, protein engineering, and single-molecule biophysics have illuminated the sequence determinants of folding, binding specificity, and biological function for DNA-binding proteins and ATP-fueled machines that forcibly unfold native proteins as a prelude to degradation. In addition to structure-function relationships, these studies provide information about folding intermediates, mutations that accelerate folding, slow unfolding, and stabilize proteins against denaturation, show how new binding specificities and folds can evolve, and reveal strategies that proteolytic machines use to recognize, unfold, and degrade thousands of distinct substrates.