title: Structural heterogeneity of 6 M GdmCl-denatured proteins: implications for the mechanism of protein folding.
abstract: An in vitro experiment with protein folding is typically initiated with 6 M GdmCl-denatured proteins, which are generally considered fully unfolded. However, studies conducted by various laboratories have shown that many 6 M GdmCl-denatured proteins are structurally heterogeneous and still retain nativelike residual structures. The extent of conformational heterogeneity of the 6 M GdmCl-denatured protein has significant implications for the folding landscape as well as the interpretation of the observed early stage folding mechanism. Using the method of disulfide scrambling, we are able to gain rough insight into the diverse structural properties of 6 M GdmCl-denatured proteins. It demonstrates that most 6 M GdmCl-denatured proteins are approximately fully denatured, but partially unfolded. Most of them comprise diverse conformational isomers. We review here the cumulative evidence obtained from various laboratories and also provide experimental data obtained in our laboratory.
authors.affiliation: Department of Biochemistry and Molecular Biology, Research Center for Protein Chemistry, Brown Foundation Institute of Molecular Medicine, University of Texas, Houston, Texas 77030, USA. Rowen.Chang@uth.tmc.edu
authors.forename: Jui-Yoa
authors.initials: JY
authors.lastname: Chang
mesh_terms: D000818:Animals; D060829:Arthropod Proteins; D004220:Disulfides / Q000737:chemistry / Q000378:metabolism; D015951:Factor Xa / Q000737:chemistry / Q000378:metabolism; D065427:Factor Xa Inhibitors; D019791:Guanidine / Q000737:chemistry*; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D011489:Protein Denaturation; D017510:Protein Folding; D013329:Structure-Activity Relationship; D013987:Ticks
chemical_list: D060829:Arthropod Proteins; D004220:Disulfides; D065427:Factor Xa Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; C063967:tick anticoagulant peptide; D015951:Factor Xa; D019791:Guanidine