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Cytotoxic Helix-Rich Oligomer Formation by Melittin and Pancreatic Polypeptide

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Title Cytotoxic Helix-Rich Oligomer Formation by Melittin and Pancreatic Polypeptide
 
Creator SINGH, PK
GHOSH, D
TEWARI, D
MOHITE, GM
CARVALHO, E
JHA, NN
JACOB, RS
SAHAY, S
BANERJEE, R
BERA, AK
MAJI, SK
 
Subject ALPHA-SYNUCLEIN AGGREGATION
BETA-PROTEIN FIBRILLOGENESIS
SOLUBLE AMYLOID OLIGOMERS
ATOMIC-FORCE MICROSCOPY
PARKINSONS-DISEASE
ALZHEIMERS-DISEASE
CELL-SURFACE
MISFOLDING DISEASES
FLUORESCENT-PROBE
COMMON MECHANISM
 
Description 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 asynuclein (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.
 
Publisher PUBLIC LIBRARY SCIENCE
 
Date 2016-01-15T10:12:45Z
2016-01-15T10:12:45Z
2015
 
Type Article
 
Identifier PLOS ONE, 10(3)
1932-6203
http://dx.doi.org/10.1371/journal.pone.0120346
http://dspace.library.iitb.ac.in/jspui/handle/100/18340
 
Language en