Interactions Between a Helical Residue and Tertiary Structures: Helix Propensities in Small Peptides and in Native Proteins

Qian, Hong; Chan, Sunney I.

doi:10.1006/jmbi.1996.0459

Cited by 22 publications

(10 citation statements)

References 34 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At lower pH*, tau-C does not adopt any preferential secondary structure in water because of the overwhelming free energy contribution from solvent interactions with isolated oligopeptides. Resorting to aqueous -organic solvent mixtures, such as TFE/water, to overcome this free energy barrier is a common practice in structural studies of peptides, in order to highlight the structural propensities encoded by their primary sequence [49]. By following this approach, the previously predicted h-helix tendency of tau-C [20] is indeed observed.…”

Section: Discussionmentioning

confidence: 99%

The solution structure of theC-terminal segment of tau protein

et al. 2000

View full text Add to dashboard Cite

Pathological changes in the microtubule associated protein tau, leading to tau‐containing filamentous lesions, are a major hallmark common to many types of human neurodegenerative diseases, including Alzheimer's disease (AD). No structural data are available which could rationalize the extensive conformational changes that occur when tau protein is converted to Alzheimer's paired helical filaments (PHF). The C‐terminal portion of tau plays a crucial role in the aggregation of tau into PHF and in the truncation process that generates cytotoxic segments of tau. Therefore, we investigated the solution structure of the hydrophobic C‐terminal segment 423–441 of tau protein (PQLATLADEVSASLAKQGL) by 1H 2D NMR spectroscopy. The peptide displays the typical NMR evidence consistent with a α‐helix geometry with a stabilizing C‐capping motif. The reported data represent the first piece of structural information on an important portion of the molecule and can have implications towards the understanding of its pathophysiology. Copyright © 2000 European Peptide Society and John Wiley & Sons, Ltd.

show abstract

Section: Discussionmentioning

confidence: 99%

The solution structure of theC-terminal segment of tau protein

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Our peptide results confirm that the problem does not lie in helix-coil theory. One recent attempt to explain the discrepancy between propensities measured in peptides and proteins was made by Qian and Chan (33). In their model, protein-based systems and isolated peptides should only give identical measures of helix propensity when helix formation and global protein folding are tightly coupled.…”

Section: Figmentioning

confidence: 99%

A direct comparison of helix propensity in proteins and peptides

Myers

Pace

Scholtz

1997

Proc. Natl. Acad. Sci. U.S.A.

125

122

View full text Add to dashboard Cite

ABSTRACT␣-Helical secondary structure occurs widely in globular proteins and its formation is a key step in their folding. As a consequence, understanding the energetics of helix formation is crucial to understanding protein folding and stability. We have measured the helix propensities of the nonpolar amino acids for an ␣-helix in an intact protein, ribonuclease T 1 , and for a 17-residue peptide with a sequence identical to that of the ␣-helix in the protein. The helix propensities are in excellent agreement. This shows that when compared in the same sequence context, the helix propensities of the nonpolar amino acids are identical in helical peptides and intact proteins, and that conclusions based on studies of the helix-to-coil transitions of peptides may, in favorable cases, be directly applicable to proteins. Our helix propensities based on ribonuclease T 1 are in good agreement with those from similar studies of barnase and T4 lysozyme. In contrast, our helix propensities differ substantially from those derived from studies of alanine-stabilized or salt bridge-stabilized model ␣-helical peptides.Predicting the three-dimensional structure of a protein from its amino acid sequence and gaining a detailed understanding of the mechanism of protein folding remain two of the most difficult, unsolved problems in biochemistry. In both cases, understanding the many forces that contribute to the conformational stability of a protein and their interplay is a major difficulty. One approach to this problem is to uncouple the formation of secondary structure from overall protein folding by studying the factors that influence secondary structure formation in model peptides. ␣-Helices are of primary interest because they occur widely in proteins and the isolated peptides often form helical structures in solution so that they can be used as convenient models for protein folding and stability (1-5). Although model ␣-helical peptides have been studied in detail, the relevance of these models to the folding of intact proteins has not been carefully explored. Here we present a direct comparison of the helix propensity of the nonpolar amino acids measured in an ␣-helix in an intact protein, and in an ␣-helical peptide with the identical sequence.Ribonuclease T 1 (RNase T 1 ) is a small (104 residue), monomeric protein, which has proven to be a useful model for the study of protein folding and stability (6). RNase T 1 is an ␣ϩ␤ class protein with several strands of ␤-sheet packed against a relatively long (17 residues and 4.5 turns) ␣-helix, forming a hydrophobic core (7). The sequence of the single ␣-helix in wild-type RNase T 1 is: SSDVSTAQAAGYKLHED, which corresponds to Ser-13 through Asp-29 in the intact protein (Fig. 1). The helical portion of the RNase T1 protein has a near ideal site at which to measure helix propensities: alanine 21 is in the exact center of the helix, on the solvent exposed face, and the side chains of residues (i, iϩ3) and (i, iϩ4), which could interact with residues at position 21 are all involved in ...

show abstract

“…The mutation glycine 23 to alanine in ribonuclease T 1 (RNase T 1 ) causes a peptide corresponding to the R-helix in the protein (residues [13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] to show significant helix formation in aqueous solution (21,22). This allows a direct comparison of helix propensity in peptides and proteins with identical sequence.…”

mentioning

confidence: 99%

Helix Propensities Are Identical in Proteins and Peptides

1997

Biochemistry

185

175

View full text Add to dashboard Cite

Our understanding of the factors stabilizing alpha-helical structure has been greatly enhanced by the study of model alpha-helical peptides. However, the relationship of these results to the folding of helices in intact proteins is not well characterized. Helix propensities measured in model peptides are not in good agreement with those from proteins. In order to address these questions, we have measured helix propensities in the alpha-helix of ribonuclease T1 and a helical peptide of identical sequence. We have previously demonstrated excellent agreement between peptide and protein for the nonpolar amino acids [Myers, J. K., Pace, C. N., and Scholtz, J. M. (1997) Proc. Natl. Acad. Sci. U.S.A. 94, 2833-2837]. Most other amino acids also show good agreement, although certain polar amino acids are exceptions. Helix propensities measured in the ribonuclease T1 peptide/protein are compared with those measured in other systems. Reasonable agreement is found between most systems; however, our propensities differ substantially from those measured in several model peptide systems. Alanine-based peptides overestimate the propensity differences by a factor of 2, and host/guest experiments underestimate them by a factor of 2-3.

show abstract

Interactions Between a Helical Residue and Tertiary Structures: Helix Propensities in Small Peptides and in Native Proteins

Cited by 22 publications

References 34 publications

The solution structure of theC-terminal segment of tau protein

The solution structure of theC-terminal segment of tau protein

A direct comparison of helix propensity in proteins and peptides

Helix Propensities Are Identical in Proteins and Peptides

Contact Info

Product

Resources

About