27 research outputs found
Unfolded, misfolded, and self-organized short alanine-rich peptides: implications for fundamental science, human disease, and biotechnology
Protein folding is the reversible transition by which an unordered polypeptide chain attains its functional 3-D native structure. A detailed understanding of the principles which govern the protein folding process, such as how sequence codes for structure, remains elusive. Achieving a complete picture of the folding process requires information regarding structural preferences in the unfolded state. Moreover, understanding the principles which govern protein aggregation is of significant biomedical and biotechnological importance. Herein, short alanine-based peptides are used as model systems for studying both the structural preferences in the unfolded state as well as protein aggregation in relation to human disease, and exploitation of the self-assembly process for various biotechnological applications.It is now a central dogma of protein science that the unfolded state is not conformationally random, as was originally believed, but that, instead, residual structure exists. Here, we elucidate the conformational propensities of alanine in the unfolded state using short alanine-rich peptides as model systems. The intrinsic conformational propensities of alanine, as well as nearest neighbor effects are illuminated using various vibrational spectroscopic methods, combined with NMR results.Protein and peptide aggregation is affiliated with various seemingly unrelated diseases, including several neurodegenerative diseases and the systemic amyloidoses. It is of current belief that aggregation is a general feature of the protein energy landscape, suggesting that the various unrelated human pathologies linked to protein aggregation are linked by common principles. Herein, fibril formation of a short alanine-based peptide with no known disease affiliation is probed by vibrational circular dichroism (VCD) spectroscopy. In particular, it is demonstrated that peptide fibrils give rise to VCD intensity enhancement, illustrating the use of the technique as a novel means to probe aggregation kinetics.In addition to the biomedical relevance, protein and peptide self-assembly can be exploited as a means of constructing biomaterials with inherent biofunctionality. In this regard, oligopeptide-based hydrogels have shown potential as drug delivery systems and tissue engineering scaffolds. Herein, the unique properties of a novel class of self-assembling alanine-rich oligoopeptides are presented. In particular, it is demonstrated that conformational instability can be exploited to tune the physicochemical properties of hydrogels formed by such systems, for the potential use in various biotechnological applications.Ph.D., Physical Chemistry -- Drexel University, 201
Comment on Spracklandus Hoser, 2009 (Reptilia, Serpentes, ELAPIDAE): request for confirmation of the availability of the generic name and for the nomenclatural validation of the journal in which it was published (Case 3601; see BZN 70: 234â237; 71: 30â38, 133â135, 181â182, 252â253)
Elevational Patterns of Species Richness, Range and Body Size for Spiny Frogs
Quantifying spatial patterns of species richness is a core problem in biodiversity theory. Spiny frogs of the subfamily Painae (Anura: Dicroglossidae) are widespread, but endemic to Asia. Using spiny frog distribution and body size data, and a digital elevation model data set we explored altitudinal patterns of spiny frog richness and quantified the effect of area on the richness pattern over a large altitudinal gradient from 0â5000 m a.s.l. We also tested two hypotheses: (i) the Rapoport's altitudinal effect is valid for the Painae, and (ii) Bergmann's clines are present in spiny frogs. The species richness of Painae across four different altitudinal band widths (100 m, 200 m, 300 m and 400 m) all showed hump-shaped patterns along altitudinal gradient. The altitudinal changes in species richness of the Paini and Quasipaini tribes further confirmed this finding, while the peak of Quasipaini species richness occurred at lower elevations than the maxima of Paini. The area did not explain a significant amount of variation in total, nor Paini species richness, but it did explain variation in Quasipaini. Five distinct groups across altitudinal gradient were found. Species altitudinal ranges did not expand with an increase in the midpoints of altitudinal ranges. A significant negative correlation between body size and elevation was exhibited. Our findings demonstrate that Rapoport's altitudinal rule is not a compulsory attribute of spiny frogs and also suggest that Bergmann's rule is not generally applicable to amphibians. The study highlights a need to explore the underlying mechanisms of species richness patterns, particularly for amphibians in macroecology
Recommended from our members
The bii4africa dataset of faunal and floral population intactness estimates across Africaâs major land uses
Sub-Saharan Africa is under-represented in global biodiversity datasets, particularly regarding the impact of land use on speciesâ population abundances. Drawing on recent advances in expert elicitation to ensure data consistency, 200 experts were convened using a modified-Delphi process to estimate âintactness scoresâ: the remaining proportion of an âintactâ reference population of a species group in a particular land use, on a scale from 0 (no remaining individuals) to 1 (same abundance as the reference) and, in rare cases, to 2 (populations that thrive in human-modified landscapes). The resulting bii4africa dataset contains intactness scores representing terrestrial vertebrates (tetrapods: ±5,400 amphibians, reptiles, birds, mammals) and vascular plants (±45,000 forbs, graminoids, trees, shrubs) in sub-Saharan Africa across the regionâs major land uses (urban, cropland, rangeland, plantation, protected, etc.) and intensities (e.g., large-scale vs smallholder cropland). This dataset was co-produced as part of the Biodiversity Intactness Index for Africa Project. Additional uses include assessing ecosystem condition; rectifying geographic/ taxonomic biases in global biodiversity indicators and maps; and informing the Red List of Ecosystems
Light-Triggered Disassembly of Amyloid Fibrils
There is growing demand for novel methods that could
render the
controlled disassembly of higher-order structures formed, for example,
by peptides. Herein, we demonstrate such a method based on the application
of a photocaged variant of the amino acid lysine, namely, lysÂ(Nvoc).
Specifically, we introduce lysÂ(Nvoc) into the primary sequence of
the amyloidogenic peptide, AÎČ<sub>16â22</sub>, at a position
where the native side chain is known to play a key role in fibril
formation via hydrophobic interactions. Both AFM and infrared spectroscopic
measurements indicate that the resultant AÎČ<sub>16â22</sub> mutant is able to form fibrils whereas, more importantly, the fibrils
thus formed can be completely disassembled upon irradiation with near-UV
light, which cleaves the photolabile Nvoc moiety and triggers the
restoration of the lysine side chain. These results suggest that the
generation of a single charge in a highly hydrophobic region of the
fibrils is sufficient to promote their dissociation. Thus, we envisage
that the current approach will find useful applications wherein controlled
structural disassembly or content release is required
Thermodynamic Instability of A Self-Assembled 16-Residue Alanine-Based Oligopeptide in Aqueous Media: Hydrogel, Fibril, and Beaded Filament Formation
The Utilization of the Anomalous Intensity Enhancement of the Amide I Couplet for Probing the Formation of Peptide Fibrils in Solution
Conformational Instability, Aggregation, and Hydrogel formation of a 16-Residue Alanine-Based Peptide in Aqueous Media
Self-aggregation of a polyalanine octamer promoted by its C-terminal tyrosine and probed by a strongly enhanced vibrational circular dichroism signal
The eight-residue alanine oligopeptide Ac-A4KA2Y-NH2 (AKY8) was found to form amyloid-like fibrils upon incubation at room temperature in acidified aqueous solution at peptide concentrations \u3e10 mM. The fibril solution exhibits an enhanced vibrational circular dichroism (VCD) couplet in the amide IâČ band region that is nearly 2 orders of magnitude larger than typical polypeptide/protein signals in this region. The UV-CD spectrum of the fibril solution shows CD in the region associated with the tyrosine side chain absorption. A similar peptide, Ac-A4KA2-NH2 (AK7), which lacks a terminal tyrosine residue, does not aggregate. These results suggest a pivotal role for the C-terminal tyrosine residue in stabilizing the aggregation state of this peptide. It is speculated that interactions between the lysine and tyrosine side chains of consecutive strands in an antiparallel arrangement (e.g., cationâÏ interactions) are responsible for the stabilization of the resulting fibrils. These results offer considerations and insight regarding the de novo design of self-assembling oligopeptides for biomedical and biotechnological applications and highlight the usefulness of VCD as a tool for probing amyloid fibril formation