title: Self-assembly of a nine-residue amyloid-forming peptide fragment of SARS corona virus E-protein: mechanism of self aggregation and amyloid-inhibition of hIAPP.
abstract: Molecular self-assembly, a phenomenon widely observed in nature, has been exploited through organic molecules, proteins, DNA, and peptides to study complex biological systems. These self-assembly systems may also be used in understanding the molecular and structural biology which can inspire the design and synthesis of increasingly complex biomaterials. Specifically, use of these building blocks to investigate protein folding and misfolding has been of particular value since it can provide tremendous insights into peptide aggregation related to a variety of protein misfolding diseases, or amyloid diseases (e.g., Alzheimer's disease, Parkinson's disease, type-II diabetes). Herein, the self-assembly of TK9, a nine-residue peptide of the extra membrane C-terminal tail of the SARS corona virus envelope, and its variants were characterized through biophysical, spectroscopic, and simulated studies, and it was confirmed that the structure of these peptides influences their aggregation propensity, hence, mimicking amyloid proteins. TK9, which forms a beta-sheet rich fibril, contains a key sequence motif that may be critical for beta-sheet formation, thus making it an interesting system to study amyloid fibrillation. TK9 aggregates were further examined through simulations to evaluate the possible intra- and interpeptide interactions at the molecular level. These self-assembly peptides can also serve as amyloid inhibitors through hydrophobic and electrophilic recognition interactions. Our results show that TK9 inhibits the fibrillation of hIAPP, a 37 amino acid peptide implicated in the pathology of type-II diabetes. Thus, biophysical and NMR experimental results have revealed a molecular level understanding of peptide folding events, as well as the inhibition of amyloid-protein aggregation are reported.
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700 054, India.
authors.forename: Anirban
authors.initials: A
authors.lastname: Ghosh
authors.affiliation: Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA.
authors.forename: Amit S
authors.initials: AS
authors.lastname: Pithadia
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700 054, India.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Bhat
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700 054, India.
authors.forename: Supriyo
authors.initials: S
authors.lastname: Bera
authors.affiliation: School of Nanoscience and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Midya
authors.affiliation: Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA.|Biophysics, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA.|Department of Biological Chemistry, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Fierke
authors.affiliation: Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA.|Biophysics, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA.
authors.forename: Ayyalusamy
authors.initials: A
authors.lastname: Ramamoorthy
authors.affiliation: Department of Biophysics, Bose Institute, P-1/12 CIT Scheme VII (M), Kolkata 700 054, India.|Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA.|Biophysics, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA.
authors.forename: Anirban
authors.initials: A
authors.lastname: Bhunia
mesh_terms: D000682:Amyloid / Q000737:chemistry / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D058228:Islet Amyloid Polypeptide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D017510:Protein Folding; D017433:Protein Structure, Secondary; D013050:Spectrometry, Fluorescence; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism; D000086082:Viroporin Proteins
chemical_list: D000682:Amyloid; C501689:E protein, SARS coronavirus; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; D014759:Viral Envelope Proteins; D000086082:Viroporin Proteins