Amyloidogenic Properties of Peptides Derived from the VHL Tumor Suppressor Protein.

The von Hippel-Lindau tumor suppressor protein (pVHL) is involved in maintaining cellular oxygen homeostasis through the regulated degradation of HIF-α. The intrinsically disordered nature of pVHL makes it prone to aggregation that impairs its function, and this is further aggravated in mutant versions of the protein, thus promoting tumor development. By using in silico analysis, we predicted six peptide fragments from pVHL to be amyloidogenic. This was verified for two of the peptides by biophysical approaches, which demonstrated self-assembly and formation of β-sheet-rich aggregates, which, under transmission electron microscopy, atomic force microscopy, and X-ray diffraction, displayed typical fibrillar amyloid characteristics. These motifs may serve as proxies for exploring the nature of pVHL aggregation. © 2021 Wiley-VCH GmbH.

Citation

Vijay Kumar, Guru Krishna Kumar Viswanathan, Krittika Ralhan, Ehud Gazit, Daniel Segal. Amyloidogenic Properties of Peptides Derived from the VHL Tumor Suppressor Protein. ChemMedChem. 2021 Dec 06;16(23):3565-3568

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PMID: 34431623

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