title: Cytotoxic helix-rich oligomer formation by melittin and pancreatic polypeptide.
abstract: Conversion of amyloid fibrils by many peptides/proteins involves cytotoxic helix-rich oligomers. However, their toxicity and biophysical studies remain largely unknown due to their highly dynamic nature. To address this, we chose two helical peptides (melittin, Mel and pancreatic polypeptide, PP) and studied their aggregation and toxicity. Mel converted its random coil structure to oligomeric helical structure upon binding to heparin; however, PP remained as helix after oligomerization. Interestingly, similar to Parkinson's associated α-synuclein (AS) oligomers, Mel and PP also showed tinctorial properties, higher hydrophobic surface exposure, cellular toxicity and membrane pore formation after oligomerization in the presence of heparin. We suggest that helix-rich oligomers with exposed hydrophobic surface are highly cytotoxic to cells irrespective of their disease association. Moreover as Mel and PP (in the presence of heparin) instantly self-assemble into stable helix-rich amyloidogenic oligomers; they could be represented as models for understanding the biophysical and cytotoxic properties of helix-rich intermediates in detail.
authors: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India.
authors: Pradeep K
authors: PK
authors: Singh
authors: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India.
authors: Dhiman
authors: D
authors: Ghosh
authors: Department of Biotechnology, IIT Madras, Chennai, Tamil Nadu, India.
authors: Debanjan
authors: D
authors: Tewari
authors: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India.
authors: Ganesh M
authors: GM
authors: Mohite
authors: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India.
authors: Edmund
authors: E
authors: Carvalho
authors: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India.
authors: Narendra Nath
authors: NN
authors: Jha
authors: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India.
authors: Reeba S
authors: RS
authors: Jacob
authors: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India.
authors: Shruti
authors: S
authors: Sahay
authors: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India.
authors: Rinti
authors: R
authors: Banerjee
authors: Department of Biotechnology, IIT Madras, Chennai, Tamil Nadu, India.
authors: Amal K
authors: AK
authors: Bera
authors: Department of Biosciences and Bioengineering, IIT Bombay, Mumbai, Maharashtra, India.
authors: Samir K
authors: SK
authors: Maji
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001516:Bees; D002460:Cell Line; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008555:Melitten / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry / Q000378:metabolism*; D010191:Pancreatic Polypeptide / Q000737:chemistry / Q000378:metabolism*; D066329:Protein Aggregates; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D009498:Neurotoxins; D066329:Protein Aggregates; D008555:Melitten; D010191:Pancreatic Polypeptide; D006493:Heparin