Amyloid Fiber Formation and Membrane Disruption are Separate Processes Localized in Two Distinct Regions of IAPP, the Type-2-Diabetes-Related Peptide Export

@article{citeulike:4305993, abstract = {Aggregation of Islet Amyloid Polypeptide (IAPP) has been implicated in the development of type II diabetes. Because IAPP is a highly amyloidogenic peptide, it has been suggested that the formation of IAPP amyloid fibers causes disruption of the cellular membrane and is responsible for the death of β-cells during type II diabetes. Previous studies have shown that the N-terminal 1−19 region, rather than the amyloidogenic 20−29 region, is primarily responsible for the interaction of the IAPP peptide with membranes. Liposome leakage experiments presented in this study confirm that the pathological membrane disrupting activity of the full-length hIAPP is also shared by hIAPP1−19. The hIAPP1−19 fragment at a low concentration of peptide induces membrane disruption to a near identical extent as the full-length peptide. At higher peptide concentrations, the hIAPP1−19 fragment induces a greater extent of membrane disruption than the full-length peptide. Similar to the full-length peptide, hIAPP1−19 exhibits a random coil conformation in solution and adopts an α-helical conformation upon binding to lipid membranes. However, unlike the full-length peptide, the hIAPP1−19 fragment did not form amyloid fibers when incubated with POPG vesicles. These results indicate that membrane disruption can occur independently from amyloid formation in IAPP, and the sequences responsible for amyloid formation and membrane disruption are located in different regions of the peptide.}, author = {Brender, Jeffrey R. and Lee, Edgar L. and Cavitt, Marchello A. and Gafni, Ari and Steel, Duncan G. and Ramamoorthy, Ayyalusamy}, citeulike-article-id = {4305993}, citeulike-linkout-0 = {http://dx.doi.org/10.1021/ja710484d}, citeulike-linkout-1 = {http://pubs.acs.org/doi/abs/10.1021/ja710484d}, day = {1}, doi = {10.1021/ja710484d}, journal = {Journal of the American Chemical Society}, keywords = {amylin, amyloid, diabetes, iapp}, month = {May}, number = {20}, pages = {6424--6429}, posted-at = {2009-04-14 05:51:09}, priority = {5}, title = {Amyloid Fiber Formation and Membrane Disruption are Separate Processes Localized in Two Distinct Regions of IAPP, the Type-2-Diabetes-Related Peptide}, url = {http://dx.doi.org/10.1021/ja710484d}, volume = {130}, year = {2008} }

TY - JOUR ID - citeulike:4305993 L3 - citeulike-article-id:4305993 N2 - Aggregation of Islet Amyloid Polypeptide (IAPP) has been implicated in the development of type II diabetes. Because IAPP is a highly amyloidogenic peptide, it has been suggested that the formation of IAPP amyloid fibers causes disruption of the cellular membrane and is responsible for the death of β-cells during type II diabetes. Previous studies have shown that the N-terminal 1−19 region, rather than the amyloidogenic 20−29 region, is primarily responsible for the interaction of the IAPP peptide with membranes. Liposome leakage experiments presented in this study confirm that the pathological membrane disrupting activity of the full-length hIAPP is also shared by hIAPP1−19. The hIAPP1−19 fragment at a low concentration of peptide induces membrane disruption to a near identical extent as the full-length peptide. At higher peptide concentrations, the hIAPP1−19 fragment induces a greater extent of membrane disruption than the full-length peptide. Similar to the full-length peptide, hIAPP1−19 exhibits a random coil conformation in solution and adopts an α-helical conformation upon binding to lipid membranes. However, unlike the full-length peptide, the hIAPP1−19 fragment did not form amyloid fibers when incubated with POPG vesicles. These results indicate that membrane disruption can occur independently from amyloid formation in IAPP, and the sequences responsible for amyloid formation and membrane disruption are located in different regions of the peptide. IS - 20 JF - Journal of the American Chemical Society EP - 6429 TI - Amyloid Fiber Formation and Membrane Disruption are Separate Processes Localized in Two Distinct Regions of IAPP, the Type-2-Diabetes-Related Peptide VL - 130 SP - 6424 KW - amylin KW - amyloid KW - diabetes KW - iapp AU - Brender, Jeffrey AU - Lee, Edgar AU - Cavitt, Marchello AU - Gafni, Ari AU - Steel, Duncan AU - Ramamoorthy, Ayyalusamy PY - 2008/05/01/ UR - http://dx.doi.org/10.1021/ja710484d ER -