title: Experimental approaches to protein folding based on the concept of a slow hydrogen exchange core.
abstract: In a review of protein hydrogen exchange, we concluded that the slow exchange core is the folding core. By this we mean that the elements of secondary structure carrying the slowest exchanging backbone amides will tend to be the elements of secondary structure to fold first, that partially folded proteins will tend to be most organized in the core, and that peptides made to mimic the slow exchange core will tend to show nativelike structure. These generalizations have led us to ask several experimental questions that will be examined here: (1) In partially folded and unfolded proteins, how do the dynamics and structure of core regions differ from noncore regions? (2) Can we make protein 'core modules' as peptides corresponding to the slow exchange core? Can core modules be covalently linked to make a native state in which one conformation is significantly more stable than all other accessible conformations? (3) In a mutant perturbed outside the core, what are the effects on hydrogen exchange and folding?
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 1479 Gortner Ave. St. Paul, MN 55108, USA. clare@biosci.cbs.umn.edu
authors.forename: C
authors.initials: C
authors.lastname: Woodward
authors.forename: E
authors.initials: E
authors.lastname: Barbar
authors.forename: N
authors.initials: N
authors.lastname: Carulla
authors.forename: J
authors.initials: J
authors.lastname: Battiste
authors.forename: G
authors.initials: G
authors.lastname: Barany
mesh_terms: D000595:Amino Acid Sequence; D007611:Aprotinin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006859:Hydrogen / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009154:Mutation; D019906:Nuclear Magnetic Resonance, Biomolecular; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D011506:Proteins; D006859:Hydrogen; D007611:Aprotinin