Short alanine-based peptides may form 310-helices and not α-helices in aqueous solution

Miick, Siobhan M.; Martinez, Gary V.; Fiori, Wayne R.; Todd, A. P.; Millhauser, Glenn L.

doi:10.1038/359653a0

Cited by 224 publications

(175 citation statements)

References 22 publications

Supporting

Mentioning

154

Contrasting

Order By: Relevance

“…4, 5) was obtained with five ( P = 5) components. The first "pure" component (Cl) resembles the class C spectrum (Woody, 1985), and by the blue-shifted crossover point and the low intensity positive band of m i transition may correspond to that of a type I(II1) turn or 3,0-helix (Miick et al, 1992). The second component (C2) has all the characteristics of an a-helix (Woody, 1985); the third component (C3) was assigned to the red-shifted 0-sheet (11-0) (Stevens et al, 1968;Woody, 1985); and the fourth (C4) component closely resembles the class C' spectrum and could indicate spectra of type I1 @-turn or similar structure (Woody, 1985;.…”

Section: J Safar Et Aimentioning

confidence: 99%

Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity

et al. 1993

View full text Add to dashboard Cite

The scrapie amyloid (prion) protein (PrP27-30) is the protease-resistant core of a larger precursor (PrPsC) and a component of the infectious scrapie agent; the potential to form amyloid is a result of a posttranslational event or conformational abnormality. The conformation, heat stability, and solvent-induced conformational transitions of PrP27-30 were studied in the solid state in films by CD spectroscopy and correlated with the infectivity of rehydrated and equilibrated films. The exposure of PrP27-30 in films to 60 "C, 100 "C, and 132 "C for 30 min did not change the @-sheet secondary structure; the infectivity slightly diminished at 132 "C and correlated with a decreased solubility of PrP27-30 in sodium dodecyl sulfate (SDS), probably due to cross-linking. Exposing PrP27-30 films to formic acid (FA), trifluoroacetic acid (TFA), trifluoroethanol (TFE), hexafluoro-2-propanol (HFIP), and SDS transformed the amide CD band, diminished the mean residue ellipticity of aromatic bands, and inactivated scrapie infectivity. The convex constraint algorithm (CAA) deconvolution of the CD spectra of the solventexposed and rehydrated solid state PrP27-30 identified five common spectral components. The loss of infectivity quantitatively correlated with a decreasing proportion of native, @-pleated sheet-like secondary structure component, an increasing amount of a-helical component, and an increasingly disordered tertiary structure. The results demonstrate the unusual thermal stability of the @-sheet secondary structure of PrP27-30 protein in the solid state. The conformational perturbations of PrP27-30 parallel the changes in infectivity and suggest that the @-sheet structure plays a key role in the physical stability of scrapie amyloid and in the ability to propagate and replicate scrapie.

show abstract

Section: J Safar Et Aimentioning

confidence: 99%

Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity

et al. 1993

View full text Add to dashboard Cite

show abstract

“…Recent ESR (39,42) and NMR (43) work by Millhauser et al (41) suggests the presence of 3 10 -helix at the terminus of short alanine-based helical peptides. The authors proposed that 3 10 -helices are a relic of the folding process.…”

mentioning

confidence: 99%

UV Resonance Raman Investigation of a 3₁₀-Helical Peptide Reveals a Rough Energy Landscape

Ahmed

Asher

2006

Biochemistry

View full text Add to dashboard Cite

We used UVRRS at 194 and 204 nm excitation to examine the backbone conformation of a 13-residue polypeptide (gp41 [659][660][661][662][663][664][665][666][667][668][669][670][671] ) that has been shown by NMR to predominantly fold into a 3 10 -helix. Examination of the conformation sensitive AmIII 3 region indicates the peptide has significant populations of -turn, PPII, 3 10 -helix, and π-helix-like conformations but little R-helix. We estimate that at 1°C on average six of the 12 peptide bonds are in folded conformations (predominantly 3 10 -and π-helix), while the other six are in unfolded ( -turn/PPII) conformations. The folded and unfolded populations do not change significantly as the temperature is increased from 1 to 60°C, suggesting a unique energy landscape where the folded and unfolded conformations are essentially degenerate in energy and exhibit identical temperature dependences.An understanding of the mechanisms of protein folding will enable the de novo design of proteins with profound commercial and medical applications (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). Over the past 50 years, significant effort to elucidate protein folding and unfolding mechanisms has been expended. Part of this effort has examined the thermodynamics and kinetics of small model systems such as -hairpins (20)(21)(22) and alanine-based R-helices (23-33). These studies have provided detailed microscopic knowledge of the folding energy landscape of these isolated motifs. Theoretical simulations have suggested that 3 10 -helices and/or type III -turns may serve as intermediates in the R-helix folding pathway (34-39). The formation of kinetic intermediates such as -turn or 3 10 -helix lowers the entropic cost of nucleating the first helical residue, thus facilitating the helix folding transition (34,40,41).The 3 10 -helix is the fourth most common secondary structural motif in proteins (34-59). On average, in proteins, 3-4% of peptide residues occur in a 3 10 -helix conformation (48). The 3 10 -helix differs from an R-helix in that the tighter packing of the backbone forces the CdO‚‚‚H-N hydrogen bonds to point outward, away from the helical axis, resulting in decreased stability of the 3 10 -helix compared to that of the R-helix (25,48).Recent ESR (39, 42) and NMR (43) work by Millhauser et al. (41) suggests the presence of 3 10 -helix at the terminus of short alanine-based helical peptides. The authors proposed that 3 10 -helices are a relic of the folding process. They reasoned that nascent helices contain mixtures of unfolded and turn conformations, specifically type III turns. As folding conditions begin to favor helical structures, the type III turn conformation (a single 3 10 -helix unit) propagates; i.e., the chain adopts a 3 10 -helix conformation. As the helical domain lengthens, the R-helix conformation competes with the 3 10 -helix conformation. Finally, at longer helical lengths, the R-helix conformation dominates. Some 3 10 -helix/type III turn-like conformations may survive...

show abstract

“…However, short Ala-based peptides have been suggested to exist in a 310-helix rather than an a-helix (Miick et al, 1992), so both conformations for F4-6 may be possible. The a-helix is also favored energetically over its other variant counterparts (2.2,-, a-, and w-helices) in both right-and left-handed conformations (Ramachandran & Sasisekharan, 1968).…”

Section: Discussionmentioning

confidence: 99%

Structure of synthetic peptide analogues of an eggshell protein of Schistosoma mansoni

et al. 1993

View full text Add to dashboard Cite

The peptide (Gly-L-Tyr-L-Asp-L-Lys-L-Tyr),, referred to as F4-6, was synthesized as a model for a schistosome eggshell protein in which the Gly-Tyr-Asp-Lys-Tyr consensus sequence is repeated over 40 times. Analysis by CD, Fourier transform infrared spectroscopy, potentiometric and spectrophotometric titrations, NMR, and molecular modeling suggests that F4-6 forms some type of left-handed structure. A likely possibility appears to be a lefthanded a-helix stabilized by Lysj-Aspj+, salt bridges and possibly Aspj-Tyrj+, hydrogen bonding and Tyr-Tyr interactions. Spectroscopic studies of a number of F4-6 analogues support this conclusion. For example, substitution of D-Ala for Gly produces a peptide with enhanced left-handed helical spectral characteristics, whereas an L-Ala substitution results in a peptide with minimal structure. These studies suggest that the F4 protein from Schistosoma mansoni may be the first example of a naturally occurring protein devoid of proline and carbohydrate that forms a left-handed helix composed of L-amino acids, although alternative forms of other left-handed structures have yet to be rigorously excluded.Keywords: F4-6 peptide; Schistosoma mansoni; schistosome eggshell protein The pathology of schistosomiasis is due to the inflammatory response to the eggs of the parasitic trematode, Schistosoma mansoni (or other closely related schistosomes) lodged in the hosts' body tissues. Granulomas form around the eggs in response to soluble carbohydrate and protein antigens secreted by the eggs. When an egg is deposited by the female schistosome, it contains a fertilized ovum and 30-40 vitelline cells. Development of the miracidium larva occurs inside the eggshell lodged in the host tissues. The eggshell is formed shortly before egg laying from protein precursors secreted by the vitelline cells that subsequently become surrounded by the eggshell. These vitelline cells serve as a food supply for the developing miracidium and disappear before hatching. The secreted

show abstract

Short alanine-based peptides may form 310-helices and not α-helices in aqueous solution

Cited by 224 publications

References 22 publications

Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity

Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity

UV Resonance Raman Investigation of a 3₁₀-Helical Peptide Reveals a Rough Energy Landscape

Structure of synthetic peptide analogues of an eggshell protein of Schistosoma mansoni

Contact Info

Product

Resources

About

Short alanine-based peptides may form 310-helices and not α-helices in aqueous solution

Cited by 224 publications

References 22 publications

Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity

Thermal stability and conformational transitions of scrapie amyloid (prion) protein correlate with infectivity

UV Resonance Raman Investigation of a 310-Helical Peptide Reveals a Rough Energy Landscape

Structure of synthetic peptide analogues of an eggshell protein of Schistosoma mansoni

Contact Info

Product

Resources

About

UV Resonance Raman Investigation of a 3₁₀-Helical Peptide Reveals a Rough Energy Landscape