Amyloidogenic Properties of Peptides Derived from the VHL Tumor Suppressor Protein |
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Authors: | Dr Vijay Kumar Dr Guru Krishna Kumar Viswanathan Dr Krittika Ralhan Prof Ehud Gazit Prof Daniel Segal |
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Affiliation: | 1. Shmunis School of Biomedicine and Cancer Research, Dr. George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv–Yafo, 69978 Israel
These authors contributed equally to this work.;2. Shmunis School of Biomedicine and Cancer Research, Dr. George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv–Yafo, 69978 Israel |
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Abstract: | 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. |
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Keywords: | Amyloids Cancer Protein aggregation Tumor suppressor protein VHL protein |
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