			Home About us Contact

Structural Propensities (structural + propensity)

Distribution by Scientific Domains

Chemistry	100%

Selected Abstracts

Structural characterization of a neurotoxic threonine-rich peptide corresponding to the human prion protein ,2-helical 180,195 segment, and comparison with full-length ,2-helix-derived peptides,

JOURNAL OF PEPTIDE SCIENCE, Issue 10 2008
Luisa Ronga
Abstract The 173,195 segment corresponding to the helix 2 of the globular PrP domain is a good candidate to be one of the several ,spots' of intrinsic structural flexibility, which might induce local destabilization and concur to protein transformation, leading to aggregation-prone conformations. Here, we report CD and NMR studies on the ,2-helix-derived peptide of maximal length (hPrP[180,195]) that is able to exhibit a regular structure different from the prevalently random arrangement of other ,2-helix-derived peptides. This peptide, which has previously been shown to be affected by buffer composition via the ion charge density dependence typical of Hofmeister effects, corresponds to the C -terminal sequence of the PrPC full-length ,2-helix and includes the highly conserved threonine-rich 188,195 segment. At neutral pH, its conformation is dominated by ,-type contributions, which only very strong environmental modifications are able to modify. On TFE addition, an increase of ,-helical content can be observed, but a fully helical conformation is only obtained in neat TFE. However, linking of the 173,179 segment, as occurring in wild-type and mutant peptides corresponding to the full-length ,2-helix, perturbs these intrinsic structural propensities in a manner that depends on whether the environment is water or TFE. Overall, these results confirm that the 180,195 parental region in hPrPC makes a strong contribution to the chameleon conformational behavior of the segment corresponding to the full-length ,2-helix, and could play a role in determining structural rearrangements of the entire globular domain. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd. [source]

15N relaxation study of the amyloid ,-peptide: structural propensities and persistence length

MAGNETIC RESONANCE IN CHEMISTRY, Issue S1 2006
Jens Danielsson
Abstract The dynamics of monomeric Alzheimer A,(1,40) in aqueous solution was studied using heteronuclear NMR experiments. 15N NMR relaxation rates of amide groups report on the dynamics in the peptide chain and make it possible to estimate structural propensities from temperature-dependent relaxation data and chemical shifts change analysis. The persistence length of the polypeptide chain was determined using a model in which the influence of neighboring residue relaxation is assumed to decay exponentially as a function of distance. The persistence length of the A,(1,40) monomer was found to decrease from eight to three residues when temperature was increased from 3 to 18 °C. At 3 °C the peptide shows structural propensities that correlate well with the suggested secondary structure regions of the peptide to be present in the fibrils, and with the ,-helical structure in membrane-mimicking systems. Our data leads to a structural model for the monomeric soluble ,-peptide with six different regions of secondary structure propensities. The peptide has two regions with ,-strand propensity (residues 16,24 and 31,40), two regions with high PII-helix propensity (residues 1,4 and 11,15) and two unstructured regions with higher mobility (residues 5,10 and 25,30) connecting the structural elements. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Sensitivity of secondary structure propensities to sequence differences between ,- and ,-synuclein: Implications for fibrillation

PROTEIN SCIENCE, Issue 12 2006
Joseph A. Marsh
Abstract The synucleins are a family of intrinsically disordered proteins involved in various human diseases. ,-Synuclein has been extensively characterized due to its role in Parkinson's disease where it forms intracellular aggregates, while ,-synuclein is overexpressed in a majority of late-stage breast cancers. Despite fairly strong sequence similarity between the amyloid-forming regions of ,- and ,-synuclein, ,-synuclein has only a weak propensity to form amyloid fibrils. We hypothesize that the different fibrillation tendencies of ,- and ,-synuclein may be related to differences in structural propensities. Here we have measured chemical shifts for ,-synuclein and compared them to previously published shifts for ,-synuclein. In order to facilitate direct comparison, we have implemented a simple new technique for re-referencing chemical shifts that we have found to be highly effective for both disordered and folded proteins. In addition, we have developed a new method that combines different chemical shifts into a single residue-specific secondary structure propensity (SSP) score. We observe significant differences between ,- and ,-synuclein secondary structure propensities. Most interestingly, ,-synuclein has an increased ,-helical propensity in the amyloid-forming region that is critical for ,-synuclein fibrillation, suggesting that increased structural stability in this region may protect against ,-synuclein aggregation. This comparison of residue-specific secondary structure propensities between intrinsically disordered homologs highlights the sensitivity of transient structure to sequence changes, which we suggest may have been exploited as an evolutionary mechanism for fast modulation of protein structure and, hence, function. [source]