TAILIEUCHUNG - Báo cáo khoa học: Context-dependent effects of proline residues on the stability and folding pathway of ubiquitin

Substitution oftrans-proline at three positions in ubiquitin (residues 19, 37 and 38) produces significant context-dependent effects on protein stability (both stabilizing and destabilizing) that reflect changes to a combination of parameters including backbone flexibility, hydrophobic interactions, solvent accessibility to polar groups and intrinsic backbone conformational preferences. Kinetic analysis of thewild-type yeast protein reveals a predominant fast-folding phase which conforms to an apparent two-state folding model. . | Eur. J. Biochem. 271 4474-4484 2004 FEBS 2004 doi Context-dependent effects of proline residues on the stability and folding pathway of ubiquitin Maria D. Crespo Geoffrey W. Platt Roger Bofill and Mark S. Searle School of Chemistry Centre for Biomolecular Sciences University Park Nottingham UK Substitution of trans-proline at three positions in ubiquitin residues 19 37 and 38 produces significant contextdependent effects on protein stability both stabilizing and destabilizing that reflect changes to a combination of parameters including backbone flexibility hydrophobic interactions solvent accessibility to polar groups and intrinsic backbone conformational preferences. Kinetic analysis of the wild-type yeast protein reveals a predominant fast-folding phase which conforms to an apparent two-state folding model. Temperature-dependent studies of the refolding rate reveal thermodynamic details of the nature of the transition state for folding consistent with hydrophobic collapse providing the overall driving force. Bronsted analysis of the refolding and unfolding rates of a family of mutants with a variety of side chain substitutions for P37 and P38 reveals that the two prolines which are located in a surface loop adjacent to the C terminus of the main a-helix residues 24-33 are not significantly structured in the transition state for folding and appear to be consolidated into the native structure only late in the folding process. We draw a similar conclusion regarding position 19 in the loop connecting the N-terminal b-hairpin to the main a-helix. The proline residues of ubiquitin are passive spectators in the folding process but influence protein stability in a variety of ways. Keywords folding kinetics NMR structural analysis proline mutations protein folding pathway protein stability. Proline is unique amongst the natural amino acid residues the five-membered ring significantly reduces the flexibility of the polypeptide chain by .

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