Tyrosine-Generated Nanostructures Initiate Amyloid Cross-Seeding in Proteins Leading to a Lethal Aggregation Trap
被引:36
作者:
Anand, Bibin G.
论文数: 0引用数: 0
h-index: 0
机构:
Jawaharlal Nehru Univ, Sch Life Sci, Biophys & Biomat Res Lab, Room 310, New Delhi 110067, India
Univ Alberta, Dept Med, Edmonton, AB T6G 2G3, CanadaJawaharlal Nehru Univ, Sch Life Sci, Biophys & Biomat Res Lab, Room 310, New Delhi 110067, India
Anand, Bibin G.
[1
,2
]
论文数: 引用数:
h-index:
机构:
Prajapati, Kailash P.
[1
]
Shekhawat, Dolat S.
论文数: 0引用数: 0
h-index: 0
机构:
Jawaharlal Nehru Univ, Sch Life Sci, Biophys & Biomat Res Lab, Room 310, New Delhi 110067, India
All India Inst Med Sci, Dept Pediat, Jodhpu, Rajasthan, IndiaJawaharlal Nehru Univ, Sch Life Sci, Biophys & Biomat Res Lab, Room 310, New Delhi 110067, India
Shekhawat, Dolat S.
[1
,3
]
Kar, Karunakar
论文数: 0引用数: 0
h-index: 0
机构:
Jawaharlal Nehru Univ, Sch Life Sci, Biophys & Biomat Res Lab, Room 310, New Delhi 110067, IndiaJawaharlal Nehru Univ, Sch Life Sci, Biophys & Biomat Res Lab, Room 310, New Delhi 110067, India
Kar, Karunakar
[1
]
机构:
[1] Jawaharlal Nehru Univ, Sch Life Sci, Biophys & Biomat Res Lab, Room 310, New Delhi 110067, India
[2] Univ Alberta, Dept Med, Edmonton, AB T6G 2G3, Canada
[3] All India Inst Med Sci, Dept Pediat, Jodhpu, Rajasthan, India
Here, we show that aromatic amino acid tyrosine, under a physiologically mimicking condition, readily forms amyloid-like entities that can effectively drive aggregation of different globular proteins and aromatic residues. Tyrosine self assembly resulted in the formation of cross-beta rich regular fibrils as well as spheroidal oligomers. Computational data suggest intermolecular interaction between specifically oriented tyrosine molecules mediated through pi-pi stacking and H-bonding interactions, mimicking a cross-beta-like architecture. Both individual protein samples and mixed protein samples underwent aggregation in the presence of tyrosine fibrils, confirming the occurrence of amyloid cross-seeding. The surface of the tyrosine's amyloid like entities was predicted to trap native protein structures, preferably through hydrophobic and electrostatic interactions initiating an aggregation event. Because tyrosine is a precursor to vital neuromodulators, the inherent cross-seeding potential of the tyrosine fibrils may have direct relevance to amyloid-linked pathologies.