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Amyloiddeposits of fibrillar human amylin (hA) in the pancreas may be a causative factor in type-2 diabetes. A detailed comparison of in vitro fibril formation by full-length hA(1–37) versus fragments of this peptide—hA(8–37) and hA(20–29)—is presented. Circular dichroism spectroscopy revealed that fibril formation was accompanied by a conformational change: random coil to β-sheet/α-helical structure. Fibril morphologies were visualized by electron microscopy and displayed a remarkable diversity. hA(20–29) formed flat ribbons consisting of numerous 3.6-nm-wide protofibrils. In contrast, hA(1–37) and hA(8–37) formed polymorphic higher order fibrils by lateral association and/or coiling together of 5.0-nm-wide protofibril subunits. For full-length hA(1–37), the predominant fibril type contained three protofibrils and for hA(8–37), the predominant type contained two protofibrils. Polymerization was also monitored …