Rules for α-Helix Termination by Glycine

Aurora, Rajeev; Srinivasan, R.; Rose, George D.

doi:10.1126/science.8178170

Cited by 281 publications

(310 citation statements)

References 49 publications

Supporting

Mentioning

297

Contrasting

Unclassified

Order By: Relevance

“…53,59,60 As the only achiral amino acid among all the proteinogenic ones, glycine frequently appears at the termination of α-helix as helix break. 54 So far, hardly any achiral glycine derivatives have been found to form helical structures. In this paper, we designed a long chain glycine derivative with N-fluorenyl-9-methoxycarbonyl (Fmoc) moiety, abbreviated as FGC18, and investigated their self-assembly in different temperatures and concentration.…”

Section: ■ Introductionmentioning

confidence: 99%

Hierarchical Self-Assembly of Achiral Amino Acid Derivatives into Dendritic Chiral Nanotwists

et al. 2012

View full text Add to dashboard Cite

ABSTRACT:The organogel formation and self-assembly of a glycine-based achiral molecule were investigated. It has been found that the compound could gel organic solvents either at a lower temperature with lower concentration or at room temperature with higher concentration, which showed different self-assembled nanostructures. At a low temperature of −15°C, the compound self-assembled into fibrous structures, whereas it formed distinctive flat microbelts at room temperature. When the organogel with nanofibers formed at −15°C was brought into an ambient condition, chiral twist nanostructures were immediately evolved, which subsequently transferred to a giant microbelt through a hierarchical dendritic twist with the time. Although the compound is achiral, it formed chiral twist with both left-and right-handed twist structures simultaneously. When a trace analogical chiral trigger, L-alanine or D-alanine derivative, was added, a complete homochiral dendritic twist was obtained. Interestingly, a reverse process, i.e. the transformation of the microbelts into twists, could occur upon dilution of the organogel with microbelt structure. During the dilution, both left-and right-handed chiral twists could be formed again. Interestingly, the same branch from the microbelt formed the twist with the same handedness. A combination of the density functional theory (DFT), molecular mechanics (MM), and molecular dynamics (MD) simulations demonstrates that the temperature-induced twisting of the bilayer is responsible for the morphological transformation and evolution of the dendrite twist. This research sheds new light on the hierarchical transformation of the chiral structures from achiral molecules via controlled self-assembly.

show abstract

Section: ■ Introductionmentioning

confidence: 99%

Hierarchical Self-Assembly of Achiral Amino Acid Derivatives into Dendritic Chiral Nanotwists

et al. 2012

View full text Add to dashboard Cite

show abstract

“…The C-cap motif has been described as having two different roles at the end of a helix (32). The first role is to adopt the positive φ and ψ dihedral angles and rigidify the final turn of the helix.…”

Section: Discussionmentioning

confidence: 99%

“…helices are C-caps (2, 7) rather than C′ residues (31,32). Positions at the helix ends are denoted relative to the caps as:…”

Section: Molecularmentioning

confidence: 99%

“…Empirical rules for improving capping motifs were taken from published summaries (7,8,31,32), with baseline positional occurrence frequencies (7). Negative design criteria were also applied by considering the effects of a sequence on possible alternative, offset capping positions.…”

Section: Molecularmentioning

confidence: 99%

“…In our protein structure database, about 15-20% of helices have completely classic C-cap motifs; 33% as listed by Aurora et al (32). λ has four classic C-caps (at the end of helices 1-4), or 80%, and reasons are given later as to why the absent C-cap motif at the chain C-terminus might not matter.…”

mentioning

confidence: 91%

See 2 more Smart Citations

Kinetic Role of Helix Caps in Protein Folding Is Context-Dependent

2004

View full text Add to dashboard Cite

Secondary structure punctuation through specific backbone and side chain interactions at the beginning and end of R-helices has been proposed to play a key role in hierarchical protein folding mechanisms [Baldwin, R. L., and Rose, G. D. (1999) Trends Biochem. Sci. 24, 26-33;Presta, L. G., and Rose, G. D. (1988) Science 240, 1632-1641. We have made site-specific substitutions in the N-and C-cap motifs of the 5-helix protein monomeric λ repressor (λ 6-85 ) and have measured the rate constants for folding and unfolding of each variant. The consequences of C-cap changes are strongly contextdependent. When the C-cap was located at the chain terminus, changes had little energetic and no kinetic effect. However, substitutions in a C-cap at the boundary between helix 4 and the subsequent interhelical loop resulted in large changes to the stability and rate constants of the variant, showing a substantial kinetic role for this interior C-cap and suggesting a general kinetic role for interior helix C-caps. Statistical preferences tabulated separately for internal and terminal C-caps also show only weak residue preferences in terminal C-caps. This kinetic distinction between interior and terminal C-caps can explain the discrepancy between the near-absence of stability and kinetic effects seen for C-caps of isolated peptides versus the very strong C-cap effects seen for proteins in statistical sequence preferences and mutational energetics. Introduction of consensus, in-register N-capping motifs resulted in increased stability, accelerated folding, and slower unfolding. The kinetic measurements indicate that some of the new native-state capping interactions remain unformed in the transition state. The accelerated folding rates could result from helix stabilization without invoking a specific role for N-caps in the folding reaction.The native and denatured conformational ensembles involved in the process of protein folding are important in proper cellular function. If the native state is the functional species, then that function is lost during any time spent in the unfolded state or in the folding process. The denatured or unfolded ensemble of structures may be more susceptible to protein turnover through cellular degradation pathways. Additionally, proper cellular localization and protein trafficking is often coupled to the folding process. A detailed understanding of the medically important process of protein misfolding and aggregation requires better molecular characterization of kinetic folding mechanisms.Each residue in a protein does not have an equal role in the folding process. Several studies have shown that often only a small subset of residues attain nativelike structure in the transition state (3-6). In this paper, we consider the role of helix termini in protein folding by determining the kinetic consequences of site-specific substitutions in helix N-and C-cap structural motifs.Helix N-and C-cap residues are found at the beginning and end of helices, ending the regular i to i + 4 hydrogen bond pattern ...

show abstract

Helical fold prediction for the cyclin box

Jf¹

1996

Proteins

View full text Add to dashboard Cite

Rules for α-Helix Termination by Glycine

Cited by 281 publications

References 49 publications

Hierarchical Self-Assembly of Achiral Amino Acid Derivatives into Dendritic Chiral Nanotwists

Hierarchical Self-Assembly of Achiral Amino Acid Derivatives into Dendritic Chiral Nanotwists

Kinetic Role of Helix Caps in Protein Folding Is Context-Dependent

Helical fold prediction for the cyclin box

Contact Info

Product

Resources

About