Home About us Contact
|
Home About us Contact | ||
|
|
||
Secondary Structure Propensities (secondary + structure_propensity)
Selected Abstracts15N relaxation study of the amyloid ,-peptide: structural propensities and persistence lengthMAGNETIC RESONANCE IN CHEMISTRY, Issue S1 2006Jens 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 fibrillationPROTEIN SCIENCE, Issue 12 2006Joseph 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] | ||||||||||