Stabilities and conformations of Alzheimer's β-amyloid peptide oligomers (Aβ16–22, Aβ16–35, and Aβ10–35): Sequence effects Export

@article{citeulike:3775542, abstract = {10.1073/pnas.212206899 Previously, we have studied the minimal oligomer size of an aggregate amyloid seed and the mechanism of seed growth with a multilayer β-sheet model. Under high temperature simulation conditions, our approach can test the stability of possible amyloid forms. Here, we report our study of oligomers of Alzheimer's amyloid β-peptide (Aβ) fragments 16–22, 16–35, and 10–35 (abbreviated Aβ, Aβ, and Aβ, respectively). Our simulations indicate that an antiparallel β-sheet orientation is the most stable for the Aβ, in agreement with a solid state NMR-based model [Balbach, J. J., Ishii, Y., Antzutkin, O. N., Leapman, R. D., Rizzo, N. W., . (2000) 39, 13748–13759]. A model with twenty-four Aβ strands indicates a highly twisted fibril. Whereas the short Aβ and Aβ may exist in fully extended form, the linear parallel β-sheets for Aβ appear impossible, mainly because of the polar region in the middle of the 16–35 sequence. However, a bent double-layered hairpin-like structure (called ) with the polar region at the turn forms parallel β-sheets with higher stability. An intra-strand salt-bridge (D23-K28) stabilizes the bent hairpin-like hook structure. The bent double-β-sheet model for the Aβ similarly offers oligomer stability.}, author = {Ma, Buyong and Nussinov, Ruth}, citeulike-article-id = {3775542}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.212206899}, citeulike-linkout-1 = {http://www.pnas.org/content/99/22/14126.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/99/22/14126.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/12391326}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=12391326}, day = {29}, doi = {10.1073/pnas.212206899}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {amyloids, short-peptides}, month = {October}, number = {22}, pages = {14126--14131}, posted-at = {2008-12-11 19:15:09}, priority = {2}, title = {Stabilities and conformations of Alzheimer's β-amyloid peptide oligomers (Aβ16–22, Aβ16–35, and Aβ10–35): Sequence effects}, url = {http://dx.doi.org/10.1073/pnas.212206899}, volume = {99}, year = {2002} }

TY - JOUR ID - citeulike:3775542 L3 - citeulike-article-id:3775542 N2 - 10.1073/pnas.212206899 Previously, we have studied the minimal oligomer size of an aggregate amyloid seed and the mechanism of seed growth with a multilayer β-sheet model. Under high temperature simulation conditions, our approach can test the stability of possible amyloid forms. Here, we report our study of oligomers of Alzheimer's amyloid β-peptide (Aβ) fragments 16–22, 16–35, and 10–35 (abbreviated Aβ, Aβ, and Aβ, respectively). Our simulations indicate that an antiparallel β-sheet orientation is the most stable for the Aβ, in agreement with a solid state NMR-based model [Balbach, J. J., Ishii, Y., Antzutkin, O. N., Leapman, R. D., Rizzo, N. W., . (2000) 39, 13748–13759]. A model with twenty-four Aβ strands indicates a highly twisted fibril. Whereas the short Aβ and Aβ may exist in fully extended form, the linear parallel β-sheets for Aβ appear impossible, mainly because of the polar region in the middle of the 16–35 sequence. However, a bent double-layered hairpin-like structure (called ) with the polar region at the turn forms parallel β-sheets with higher stability. An intra-strand salt-bridge (D23-K28) stabilizes the bent hairpin-like hook structure. The bent double-β-sheet model for the Aβ similarly offers oligomer stability. IS - 22 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 14131 TI - Stabilities and conformations of Alzheimer's β-amyloid peptide oligomers (Aβ16–22, Aβ16–35, and Aβ10–35): Sequence effects VL - 99 SP - 14126 KW - amyloids KW - short-peptides AU - Ma, Buyong AU - Nussinov, Ruth PY - 2002/10/29/ UR - http://dx.doi.org/10.1073/pnas.212206899 ER -