Fast Events in Protein Folding:  Helix Melting and Formation in a Small Peptide

Williams, Sharon; Causgrove, Timothy P.; Gilmanshin, Rudolf; Fang, Ke; Callender, Robert; Woodruff, William H.; Dyer, R. Brian

doi:10.1021/bi952217p

Cited by 611 publications

(851 citation statements)

References 44 publications

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“…15,16,18,21,22,[28][29][30][31] Experimentally, rapid laser-induced T-jump methods have allowed the first investigations of the formation of -helices. [4][5][6][7][8][9][10][11] In these studies, a rapid T-jump pulse induces a shift in the equilibrium between the coil and helix states, and the subsequent relaxation toward the new thermal equilibrium point is probed by examining all of the amide groups via either IR 4,8,11 or Raman 7 spectroscopy, or individual residues by fluorescence spectroscopy 5 or isotopeediting 9,10 techniques. However, the peptides used in these studies are rather similar.…”

Section: Introductionmentioning

confidence: 99%

Length Dependent Helix−Coil Transition Kinetics of Nine Alanine-Based Peptides

et al. 2004

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It is well-known that end caps and the peptide length can dramatically influence the thermodynamics of the helix-coil transition. However, their roles in determining the kinetics of the helix-coil transition have not been studied extensively and are less well understood. Kinetic Ising models and sequential kinetic models involving barrier crossing via diffusion all predict that the helix formation time depends monotonically on the peptide length with the relaxation time increasing with respect to increasing chain length. Here, we have studied the helix-coil transition kinetics of a series of Ala-based -helical peptides of different length (19-39 residues), with and without end caps, using time-resolved infrared spectroscopy coupled with laser-induced temperature jump (T-jump) initiation method. The helical content of these peptides was kinetically monitored by probing the amide carbonyl stretching frequencies (i.e., the amide I band) of the peptide backbone. We found that the relaxation rates for peptides with efficient end caps are more rapid than those of the corresponding peptides without good end caps. These results indicate that efficient end-capping sequences can not only stabilize preexisting helices but also promote helix formation through initiation. Furthermore, we found that the relaxation times of these peptides, following a T-jump of 1-11 °C, show rather complex behaviors as a function of the peptide length, in disagreement with theoretical predications. Theses results are not readily explained by theories in which Ala is taken to have a single helical propensity (s). However, recent studies have suggested that s depends on chain length; when this factor is considered, the mean first-passage times of the coil-to-helix transition show similar dependence on the peptide length as those observed experimentally.

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Section: Introductionmentioning

confidence: 99%

Length Dependent Helix−Coil Transition Kinetics of Nine Alanine-Based Peptides

et al. 2004

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“…To date, synthetic schemes have been successfully developed for the synthesis of R-helix-forming peptides, and much has been uncovered about their folding dynamics (6)(7)(8)(9)(10)(11)(12)(13). In contrast, only limited progress has been made toward understanding the synthesis of and the dynamics of -sheet peptides.…”

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confidence: 99%

UV Raman Studies of Peptide Conformation Demonstrate That Betanova Does Not Cooperatively Unfold

Boyden

Asher

2001

Biochemistry

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We used UV resonance Raman spectroscopy (UVRR) excited within the peptide bond π f π* electronic transitions and within the aromatic amino acid π f π* electronic transitions to examine the temperature dependence of the solution conformation of betanova, a 20-residue -sheet polypeptide [Kortemme, T., Ramirez-Alvarado, M., and Serrano, L. (1998) Science 281, 253-256]. The 206.5 nm excited UVRR enhances the amide vibrations and demonstrates that betanova has a predominantly -sheet structure between 5 and 82°C. The 229 nm excited UVRR, which probes the tyrosine and tryptophan side chain vibrations, shows an increase in the solvent exposure of the tryptophan side chains as the temperature is increased. Our results are consistent with the existence of an intermediate state similar to that calculated by Bursulaya and Brooks [Bursulaya, B. D., and Brooks, C. L. (1999) J. Am. Chem. Soc. 121, 9947-9951] and exclude the previously proposed two-state cooperative folding mechanism. Betanova's structure appears to be molten globule over the 3-82°C temperature range of our study.The completion of the human genome sequence makes available the primary sequence of all proteins synthesized by the human body. This represents only the first stage in the development of an understanding of the protein structural basis of disease. The next stage in this development requires an ability to predict the structure and function of proteins from their primary sequences. At present this is impossible, since not enough is known about the dynamics and thermodynamics of protein folding (1-5).The understanding of protein folding mechanisms is advancing as experimentalists develop better strategies for the de novo design of model peptides and better methodologies for characterizing equilibrium secondary structures, as well as the dynamics of folding. To date, synthetic schemes have been successfully developed for the synthesis of R-helix-forming peptides, and much has been uncovered about their folding dynamics (6-13). In contrast, only limited progress has been made toward understanding the synthesis of and the dynamics of -sheet peptides. Primarily, studies have focused on -hairpins rather than complete sheet structures (14-18). Successful synthesis of three-stranded -sheet structures has been accomplished only recently. However, these model peptides only form complete -sheet structures under limited conditions, in the presence of organic solvents and with the use of unnatural amino acids (19)(20)(21)(22). Thus, there remains much to learn about -sheet folding.Significant advances have also occurred in the theoretical understanding of protein folding (23-28). Such work includes molecular dynamics simulations of energy landscapes that describe folding thermodynamics. Currently, some of these models accurately predict experimental results. Thus, theory can now impact how experimental data are interpreted. It seems likely that the most powerful insights into the rules of protein folding will result from combined experimental and theoreti...

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“…F s forms an α-helix and was studied using circular dichroism (CD) as well as infrared (IR) spectroscopy. The melting temperature measured by IR was 334 K [18], whereas the CD-based studies obtained T m = 308 K [17] and T m = 303 K [19]. Computational studies of F s were also reported [20][21][22].…”

Section: Foldingmentioning

confidence: 99%

Peptide folding and aggregation studied using a simplified atomic model

Irbäck¹

2005

J. Phys.: Condens. Matter

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Abstract:Using an atomic model with a simplified sequence-based potential, the folding properties of several different peptides are studied. Both α-helical (Trp cage, F s ) and β-sheet (GB1p, GB1m2, GB1m3, Betanova, LLM) peptides are considered. The model is able to fold these different peptides for one and the same choice of parameters, and the melting behaviour of the peptides (folded population against temperature) is in very good agreement with experimental data. Furthermore, using the same model with unchanged parameters, the aggregation behaviour of a fibril-forming fragment of the Alzheimer's Aβ peptide is studied, with very promising results.

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Fast Events in Protein Folding: Helix Melting and Formation in a Small Peptide

Cited by 611 publications

References 44 publications

Length Dependent Helix−Coil Transition Kinetics of Nine Alanine-Based Peptides

Length Dependent Helix−Coil Transition Kinetics of Nine Alanine-Based Peptides

UV Raman Studies of Peptide Conformation Demonstrate That Betanova Does Not Cooperatively Unfold

Peptide folding and aggregation studied using a simplified atomic model

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