Amyloidogenic Properties of Peptides Derived from the VHL Tumor Suppressor Protein
| Autor: | Ehud Gazit, Vijay Kumar, Guru KrishnaKumar Viswanathan, Krittika Ralhan, Daniel L. Segal |
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| Rok vydání: | 2021 |
| Předmět: |
Amyloid
In silico Mutant Amyloidogenic Proteins Peptide Protein aggregation urologic and male genital diseases Biochemistry law.invention law Drug Discovery Humans Amino Acid Sequence General Pharmacology Toxicology and Pharmaceutics Pharmacology chemistry.chemical_classification Chemistry Organic Chemistry Peptide Fragments female genital diseases and pregnancy complications Cell biology Von Hippel-Lindau Tumor Suppressor Protein Molecular Medicine Suppressor Protein Multimerization Homeostasis Function (biology) |
| Zdroj: | ChemMedChem. 16:3565-3568 |
| ISSN: | 1860-7187 1860-7179 |
| DOI: | 10.1002/cmdc.202100441 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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