7YL7

Structure of hIAPP-TF-type3

Summary for 7YL7

• Entry DOI: 10.2210/pdb7yl7/pdb
• EMDB information: 33903
• Descriptor: Islet amyloid polypeptide (1 entity in total)
• Functional Keywords: hiapp, amylin, protein fibril
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 12
• Total formula weight: 46899.83

Authors

Li, D.,Zhang, X. (deposition date: 2022-07-25, release date: 2022-12-28, Last modification date: 2024-05-08)

Primary citation

Li, D.,Zhang, X.,Wang, Y.,Zhang, H.,Song, K.,Bao, K.,Zhu, P.
A new polymorphism of human amylin fibrils with similar protofilaments and a conserved core.
Iscience, 25:105705-105705, 2022

PubMed Abstract: Pancreatic amyloid deposits composed of a fibrillar form of the human islet amyloid polypeptide (hIAPP) are the pathological hallmark of type 2 diabetes (T2D). Although various cryo-EM structures of polymorphic hIAPP fibrils were reported, the underlying polymorphic mechanism of hIAPP remains elusive. Meanwhile, the structure of hIAPP fibrils with all residues visible in the fibril core is not available. Here, we report the full-length structures of two different polymorphs of hIAPP fibrils, namely slim form (SF, dimer) and thick form (TF, tetramer), formed in a salt-free environment, which share a similar ζ-shaped protofilament but differ in inter-protofilament interfaces. In the absence of salt, electrostatic interactions were found to play a dominant role in stabilizing the fibril structure, suggesting an antagonistic effect between electrostatic and hydrophobic interactions in different salt concentrations environments. Our results shed light on understanding the mechanism of amyloid fibril polymorphism.

PubMed: 36567711
DOI: 10.1016/j.isci.2022.105705

Experimental method

ELECTRON MICROSCOPY (3.3 Å)