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Polymorphic fibrillar assembly of human amylin
C S Goldsbury1, G J Cooper, K N Goldie
1School of Biological Sciences, University of Auckland, New Zealand.
Journal of Structural Biology
|June 1, 1997
Summary
Human amylin forms various fibril structures, including protofibrils and higher-order assemblies like ribbons and cables. These findings in type 2 diabetes research suggest in vitro models are valuable for understanding amyloid formation.
Area of Science:
- Biochemistry
- Structural Biology
- Diabetology
Background:
- Human amylin forms amyloid fibrils in pancreatic islets of patients with type 2 diabetes mellitus.
- Synthetic human amylin also forms fibrillar assemblies in vitro.
- Understanding the structural polymorphism of these fibrils is crucial for disease research.
Purpose of the Study:
- To characterize the structural polymorphism of human amylin fibrils formed in vitro.
- To investigate the assembly pathways of amylin protofibrils into higher-order structures.
- To determine the mass-per-length of amylin protofibrils and higher-order assemblies.
Main Methods:
- In vitro assembly of synthetic human amylin in aqueous solutions.
- Electron microscopy to observe fibril morphology and dimensions.
- Mass-per-length (MPL) measurements of different fibril structures.
Main Results:
- Identified a 5-nm protofibril as the basic structural unit.
- Observed spontaneous assembly into higher-order structures: 8-nm fibrils (two protofibrils coiled), cable-like structures (multiple protofibrils), ribbons, and sheets.
- Determined the MPL of the 5-nm protofibril to be 10 kDa/nm, with higher-order fibrils showing increments of 10 kDa/nm.
Conclusions:
- Human amylin exhibits significant structural polymorphism in its fibrillar assemblies.
- The in vitro assembly of synthetic amylin provides a model for studying amyloid formation.
- Findings contribute to understanding the structural basis of amylin amyloidosis in type 2 diabetes.