Mutagenic exploration of the cross-seeding and fibrillation propensity of Alzheimer's beta-amyloid peptide variants

@article{citeulike:1572410, abstract = {Amyloid formation is a nucleation-dependent process that is accelerated dramatically in vivo and in vitro upon addition of appropriate fibril seeds. A potent species barrier can be effective in this reaction if donor and recipient come from different biological species. This species barrier is thought to reflect differences in the amino acid sequence between seed and target polypeptide. Here we present an in vitro mutagenic cross-seeding analysis of Alzheimer's A[beta](1-40) peptide in which we mapped out the effect of systematically varied amino acid replacements on the propensity of seed-dependent amyloid fibril formation. We find that the susceptibility of different peptides toward cross-seeding relates to the intrinsic aggregation propensity of the respective polypeptide chain and, therefore, to properties such as [beta]-sheet propensity and hydrophobicity. These data imply that the seed-dependent formation of amyloid-like fibrils is affected by the intrinsic properties of the polypeptide chain in a manner that is similar to what has been described previously for aggregation reactions in general. Hence, the nucleus acts in this case as a catalyst that promotes the fibrillation of different polypeptide chains according to their intrinsic structural predilection. 10.1110/ps.062116206}, author = {Peim, Alexander and Hortschansky, Peter and Christopeit, Tony and Schroeckh, Volker and Richter, Walter and Fandrich, Marcus }, citeulike-article-id = {1572410}, doi = {http://dx.doi.org/10.1110/ps.062116206}, journal = {Protein Sci}, keywords = {amylod, cross-seeding, fibrillation}, month = {July}, number = {7}, pages = {1801--1805}, posted-at = {2007-08-17 12:55:57}, priority = {2}, title = {Mutagenic exploration of the cross-seeding and fibrillation propensity of Alzheimer's beta-amyloid peptide variants}, url = {http://dx.doi.org/10.1110/ps.062116206}, volume = {15}, year = {2006} }

TY - JOUR ID - citeulike:1572410 L3 - citeulike-article-id:1572410 TI - Mutagenic exploration of the cross-seeding and fibrillation propensity of Alzheimer's beta-amyloid peptide variants JF - Protein Sci VL - 15 IS - 7 SP - 1801 EP - 1805 N2 - Amyloid formation is a nucleation-dependent process that is accelerated dramatically in vivo and in vitro upon addition of appropriate fibril seeds. A potent species barrier can be effective in this reaction if donor and recipient come from different biological species. This species barrier is thought to reflect differences in the amino acid sequence between seed and target polypeptide. Here we present an in vitro mutagenic cross-seeding analysis of Alzheimer's A[beta](1-40) peptide in which we mapped out the effect of systematically varied amino acid replacements on the propensity of seed-dependent amyloid fibril formation. We find that the susceptibility of different peptides toward cross-seeding relates to the intrinsic aggregation propensity of the respective polypeptide chain and, therefore, to properties such as [beta]-sheet propensity and hydrophobicity. These data imply that the seed-dependent formation of amyloid-like fibrils is affected by the intrinsic properties of the polypeptide chain in a manner that is similar to what has been described previously for aggregation reactions in general. Hence, the nucleus acts in this case as a catalyst that promotes the fibrillation of different polypeptide chains according to their intrinsic structural predilection. 10.1110/ps.062116206 KW - amylod KW - cross-seeding KW - fibrillation AU - Peim, Alexander AU - Hortschansky, Peter AU - Christopeit, Tony AU - Schroeckh, Volker AU - Richter, Walter AU - Fandrich, Marcus PY - 2006/07/01/ UR - http://dx.doi.org/10.1110/ps.062116206 ER -