Autonomous subdomains in protein folding.
Proteolytic dissection of native trp repressor and horse heart cytochrome c has been used to infer some of the steps in the folding pathways of the intact proteins. For both proteins, small fragments are capable of undergoing spontaneous noncovalent association to form subdomains with native-like secondary and/or tertiary structural features, suggesting that dissection/reassembly may be a general method to gain insight into the structures of folding intermediates. The importance of this approach is its simplicity and potential applicability to studying the folding pathways of a wide range of proteins. The proteases report on the structure and dynamics of the native state, circumventing the need for prior knowledge of the structures of folding intermediates. The observation that small fragments of proteins can associated noncovalently suggests that protein folding can be viewed as an intramolecular "recognition" process. The results imply that substantial information about protein structure and folding is encoded at the level of subdomains, and that chain connectivity has only a minor role in determining the fold.
Chemistry Department, Princeton University, New Jersey 08544-1009.
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D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D003574:Cytochrome c Group / Q000737:chemistry; D006736:Horses; D015394:Molecular Structure; D009206:Myocardium / Q000737:chemistry; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012097:Repressor Proteins / Q000737:chemistry; D029968:Escherichia coli Proteins
D001426:Bacterial Proteins; D003574:Cytochrome c Group; D011506:Proteins; D012097:Repressor Proteins; C027190:TRPR protein, E coli; D029968:Escherichia coli Proteins