3D analysis of human islet amyloid polypeptide crystalline structures in Drosophila melanogaster

Autoři: Ling Xie aff001;  Xiaohong Gu aff002;  Kenta Okamoto aff003;  Gunilla T. Westermark aff002;  Klaus Leifer aff001
Působiště autorů: Department of Engineering Sciences, Applied Materials Sciences, Uppsala University, Uppsala, Sweden aff001;  Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden aff002;  Department of Biology Physics, Uppsala University, Uppsala, Sweden aff003
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223456


Expression of the Alzheimer’s disease associated polypeptide Aβ42 and the human polypeptide hormon islet amyloid polypeptide (hIAPP) and the prohormone precursor (hproIAPP) in neurons of Drosophila melanogaster leads to the formation of protein aggregates in the fat body tissue surrounding the brain. We determined the structure of these membrane-encircled protein aggregates using transmission electron microscopy (TEM) and observed the dissolution of protein aggregates after starvation. Electron tomography (ET) as an extension of transmission electron microscopy revealed that these aggregates were comprised of granular subunits having a diameter of 20 nm aligned into highly ordered structures in all three dimensions. The three dimensional (3D) lattice of hIAPP granules were constructed of two unit cells, a body centered tetragonal (BCT) and a triclinic unit cell. A 5-fold twinned structure was observed consisting of the cyclic twinning of the BCT and triclinic unit cells. The interaction between the two nearest hIAPP granules in both unit cells is not only governed by the van der Waals forces and the dipole-dipole interaction but potentially also by filament-like structures that can connect the nearest neighbors. Hence, our 3D structural analysis provides novel insight into the aggregation process of hIAPP in the fat body tissue of Drosophila melanogaster.

Klíčová slova:

Amyloid proteins – Crystal structure – Drosophila melanogaster – Fats – Protein structure – Protein structure comparison – Transmission electron microscopy – Nutrient and storage proteins


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2019 Číslo 10