Biochemical and Biophysical Research Communications, Vol.533, No.1, 125-131, 2020
Structural characterization and cryo-electron tomography analysis of human islet amyloid polypeptide suggest a synchronous process of the hIAPP(1-37) amyloid fibrillation
Revealing the aggregation and fibrillation process of variant amyloid proteins is critical for understanding the molecular mechanism of related amyloidosis diseases. Here we characterized the fibrillation morphology and kinetics of type 2 diabetes (T2D) related human islet amyloid polypeptide (hIAPR(1-37)) fibril formation process using negative staining transmission electron microscopy (NS-TEM), cryoelectron microscopy (cryo-EM) analysis, and 3D cryo-electron tomography (cryo-ET) reconstruction, together with circular dichroism (CD) and Thioflavin-T (ThT) assays. Our results showed that various amyloid fibrils can be observed at different time points of hIAPR(1-)(37) fibrillization process, while the winding of protofibrils presents in different growth stages, which suggests a synchronous process of hIAPR(1-)(37) amyloid fibrillization. This work provides insights into the understanding of hIAPR(1-)(37) amyloid aggregation process and the pathogenesis of Type 2 diabetes disease. (C) 2020 Elsevier Inc. All rights reserved.