title: Mutagenic dissection of the sequence determinants of protein folding, recognition, and machine function.
abstract: 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.
authors: Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139.
authors: Robert T
authors: RT
authors: Sauer
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D049673:History, 20th Century; D009154:Mutation; D011485:Protein Binding; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D004268:DNA-Binding Proteins; D000255:Adenosine Triphosphate
keywords: ATP-dependent unfolding; Arc repressor; ClpXP; intracellular degradation; lambda repressor; tmRNA tagging
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