Structural characterization and cryo-electron tomography analysis of human islet amyloid polypeptide suggest a synchronous process of the hIAPP1-37 amyloid fibrillation

Xueli Zhang; Dongyu Li; Xushan Zhu; Youwang Wang; Ping Zhu

doi:10.1016/j.bbrc.2020.08.088

Structural characterization and cryo-electron tomography analysis of human islet amyloid polypeptide suggest a synchronous process of the hIAPP_1-37 amyloid fibrillation

Biochem Biophys Res Commun. 2020 Nov 26;533(1):125-131. doi: 10.1016/j.bbrc.2020.08.088. Epub 2020 Sep 14.

Authors

Xueli Zhang¹, Dongyu Li², Xushan Zhu¹, Youwang Wang², Ping Zhu³

Affiliations

¹ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing, 100049, China.
² National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China.
³ National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China; Sino-Danish College, University of Chinese Academy of Sciences, Beijing, 100049, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: zhup@ibp.ac.cn.

PMID: 32943189
DOI: 10.1016/j.bbrc.2020.08.088

Abstract

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 (hIAPP_1-37) fibril formation process using negative staining transmission electron microscopy (NS-TEM), cryo-electron 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 hIAPP_1-37 fibrillization process, while the winding of protofibrils presents in different growth stages, which suggests a synchronous process of hIAPP_1-37 amyloid fibrillization. This work provides insights into the understanding of hIAPP_1-37 amyloid aggregation process and the pathogenesis of Type 2 diabetes disease.

Keywords: Amylin; Amyloid; Cryo-electron tomography; Human islet amyloid polypeptide (hIAPP); Protofibril winding.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amyloid / chemistry
Amyloid / metabolism*
Amyloid / ultrastructure
Cryoelectron Microscopy
Diabetes Mellitus, Type 2 / metabolism
Humans
Islet Amyloid Polypeptide / chemistry
Islet Amyloid Polypeptide / metabolism*
Islet Amyloid Polypeptide / ultrastructure
Peptide Fragments / chemistry
Peptide Fragments / metabolism
Peptide Fragments / ultrastructure
Protein Aggregation, Pathological / metabolism

Substances

Amyloid
Islet Amyloid Polypeptide
Peptide Fragments